@article{
 title = {Protozoal populations drive system-wide variation in the rumen microbiome},
 type = {article},
 year = {2025},
 keywords = {Metagenomics,Microbial ecology,Microbiome},
 pages = {1-17},
 volume = {16},
 websites = {https://www.nature.com/articles/s41467-025-61302-2},
 month = {7},
 publisher = {Nature Publishing Group},
 day = {7},
 id = {19f0c423-5f48-3b1e-abd5-c82a48c195c2},
 created = {2025-08-19T08:25:56.034Z},
 accessed = {2025-08-19},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-08-19T08:25:58.733Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {While rapid progress has been made to characterize the bacterial and archaeal populations of the rumen microbiome, insight into how they interact with keystone protozoal species remains elusive. Here, we reveal two distinct system-wide rumen community types (RCT-A and RCT-B) that are not strongly associated with host phenotype nor genotype but instead linked to protozoal community patterns. We leveraged a series of multi-omic datasets to show that the dominant Epidinium spp. in animals with RCT-B employ a plethora of fiber-degrading enzymes that present enriched Prevotella spp. a favorable carbon landscape to forage upon. Conversely, animals with RCT-A, dominated by genera Isotricha and Entodinium, harbor a more even distribution of fiber, protein, and amino acid metabolizers, reflected by higher detection of metabolites from both protozoal and bacterial activity. Our results indicate that microbiome variation across key protozoal and bacterial populations is interlinked, which should act as an important consideration for future development of microbiome-based technologies. Here, the authors reveal that protozoal communities shape rumen microbiome structure, offering fresh insights into how these complex communities coordinate essential metabolic tasks across multiple microbial domains.},
 bibtype = {article},
 author = {Kobel, Carl M. and Leu, Andy and Vera-Ponce de León, Arturo and Øyås, Ove and Lai, Wanxin and Altshuler, Ianina and Hagen, Live H. and Wollenberg, Rasmus D. and Søndergaard, Mads T. and Bakshani, Cassie R. and Willats, William G.T. and Nicoll, Laura and McIlroy, Simon J. and Hvidsten, Torgeir R. and Schmidt, Oliver and Greening, Chris and Tyson, Gene W. and Roehe, Rainer and Aho, Velma T.E. and Pope, Phillip B.},
 doi = {10.1038/s41467-025-61302-2},
 journal = {Nature Communications 2025 16:1},
 number = {1}
}

While rapid progress has been made to characterize the bacterial and archaeal populations of the rumen microbiome, insight into how they interact with keystone protozoal species remains elusive. Here, we reveal two distinct system-wide rumen community types (RCT-A and RCT-B) that are not strongly associated with host phenotype nor genotype but instead linked to protozoal community patterns. We leveraged a series of multi-omic datasets to show that the dominant Epidinium spp. in animals with RCT-B employ a plethora of fiber-degrading enzymes that present enriched Prevotella spp. a favorable carbon landscape to forage upon. Conversely, animals with RCT-A, dominated by genera Isotricha and Entodinium, harbor a more even distribution of fiber, protein, and amino acid metabolizers, reflected by higher detection of metabolites from both protozoal and bacterial activity. Our results indicate that microbiome variation across key protozoal and bacterial populations is interlinked, which should act as an important consideration for future development of microbiome-based technologies. Here, the authors reveal that protozoal communities shape rumen microbiome structure, offering fresh insights into how these complex communities coordinate essential metabolic tasks across multiple microbial domains.

@article{
 title = {The association between the gut microbiome and 24-h blood pressure measurements in the SCAPIS study},
 type = {article},
 year = {2025},
 keywords = {Biomarkers,Clinical microbiology},
 pages = {1-9},
 volume = {5},
 websites = {https://www.nature.com/articles/s43856-025-00980-x},
 month = {12},
 publisher = {Springer Nature},
 day = {1},
 id = {53debb51-d87b-3e21-8333-b9cf22f38a08},
 created = {2025-08-19T08:26:56.389Z},
 accessed = {2025-08-19},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-31T11:47:25.531Z},
 read = {true},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: There is mounting evidence supporting the role of the microbiota in hypertension from experimental studies and population-based studies. We aimed to investigate the relationship between specific characteristics of the gut microbiome and 24-h ambulatory blood pressure measurements. Methods: The association of gut microbial species and microbial functions, determined by shotgun metagenomic sequencing of fecal samples, with 24-h ambulatory blood pressure measurements in 3695 participants and office blood pressure was assessed in multivariable-adjusted models in 2770 participants without antihypertensive medication from the Swedish CArdioPulmonary bioImage Study. Results: Gut microbiome alpha diversity was negatively associated with diastolic blood pressure variability. Additionally, four microbial species were associated with at least one of the 24-h blood pressure traits. Streptococcus sp001556435 was associated with higher systolic blood pressure, Intestinimonas massiliensis and Dysosmobacter sp001916835 with lower systolic blood pressure, Dysosmobacter sp001916835 with lower diastolic blood pressure, and ER4 sp900317525 with lower systolic blood pressure variability. Moreover, office blood pressure data from a subsample without ambulatory blood pressure measurements replicated the association of Intestinimonas massiliensis with systolic blood pressure and Dysosmobacter sp001916835 with diastolic blood pressure. Species associated with 24-h blood pressure were linked to a similar pattern of metabolites. Conclusions: In this large cross-sectional analysis, gut microbiome alpha diversity negatively associates with diastolic blood pressure variability, and four gut microbial species associate with 24-h blood pressure traits.},
 bibtype = {article},
 author = {Lin, Yi Ting and Sayols-Baixeras, Sergi and Baldanzi, Gabriel and Dekkers, Koen F. and Hammar, Ulf and Nguyen, Diem and Nielsen, Nynne and Eklund, Aron C. and Varotsis, Georgios and Holm, Jacob B. and Nielsen, H. Bjørn and Lind, Lars and Bergström, Göran and Smith, J. Gustav and Engström, Gunnar and Ärnlöv, Johan and Sundström, Johan and Orho-Melander, Marju and Fall, Tove},
 doi = {10.1038/S43856-025-00980-X;SUBJMETA=107,308,326,53,631,692;KWRD=BIOMARKERS,CLINICAL+MICROBIOLOGY},
 journal = {Communications Medicine},
 number = {1}
}

Background: There is mounting evidence supporting the role of the microbiota in hypertension from experimental studies and population-based studies. We aimed to investigate the relationship between specific characteristics of the gut microbiome and 24-h ambulatory blood pressure measurements. Methods: The association of gut microbial species and microbial functions, determined by shotgun metagenomic sequencing of fecal samples, with 24-h ambulatory blood pressure measurements in 3695 participants and office blood pressure was assessed in multivariable-adjusted models in 2770 participants without antihypertensive medication from the Swedish CArdioPulmonary bioImage Study. Results: Gut microbiome alpha diversity was negatively associated with diastolic blood pressure variability. Additionally, four microbial species were associated with at least one of the 24-h blood pressure traits. Streptococcus sp001556435 was associated with higher systolic blood pressure, Intestinimonas massiliensis and Dysosmobacter sp001916835 with lower systolic blood pressure, Dysosmobacter sp001916835 with lower diastolic blood pressure, and ER4 sp900317525 with lower systolic blood pressure variability. Moreover, office blood pressure data from a subsample without ambulatory blood pressure measurements replicated the association of Intestinimonas massiliensis with systolic blood pressure and Dysosmobacter sp001916835 with diastolic blood pressure. Species associated with 24-h blood pressure were linked to a similar pattern of metabolites. Conclusions: In this large cross-sectional analysis, gut microbiome alpha diversity negatively associates with diastolic blood pressure variability, and four gut microbial species associate with 24-h blood pressure traits.

@article{
 title = {Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection},
 type = {article},
 year = {2025},
 keywords = {CDI,Clostridioides difficile,dysbiosis,engraftment,microbiome,microbiota-based product,pharmacodynamics,pharmacokinetics},
 volume = {17},
 websites = {https://www.tandfonline.com/doi/pdf/10.1080/19490976.2025.2520412},
 month = {12},
 publisher = {Taylor and Francis Ltd.},
 day = {31},
 id = {777be786-86f0-37f0-b889-6c36e3436c55},
 created = {2025-08-19T08:27:39.093Z},
 accessed = {2025-08-19},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-08-19T08:27:39.093Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Live microbiota therapies have shown promise in many gastrointestinal diseases, including in the prevention of recurrent Clostridioides difficile infections (rCDI); however, frameworks for their pharmacokinetic and pharmacodynamic analysis are not fully established. Fecal microbiota, live-jslm (RBL) is the first microbiota-based product approved by the US Food and Drug Administration for the prevention of rCDI and was superior to placebo in the PUNCH™ CD3 phase 3 clinical trial (NCT03244644). In this analysis, deep shotgun metagenomic sequencing was used to assess changes in gut microbiome compositions of participants and engraftment of bacterial clonal populations (i.e. strains) from RBL to recipients. Among RBL responders, gut microbiota shifted toward compositions that resembled healthy donors as early as 1 week after RBL administration; the resulting microbiota compositions included clonal populations that engrafted from RBL to recipients. Engraftment was higher in RBL responders compared with non-responders, and many clonally engrafted populations persisted for ≥ 6 months. Bacteroidia species were among the most effectively engrafted species from RBL. This study utilizes data from a large clinical trial to establish a method with high specificity for exploring clonal engraftment from microbiota-based treatments to facilitate future pharmacokinetic and pharmacodynamic analyses. Clinicaltrials Registration: NCT03244644.},
 bibtype = {article},
 author = {Claypool, Josh and Lindved, Gustav and Myers, Pernille Neve and Ward, Tonya and Nielsen, Henrik Bjørn and Blount, Ken F.},
 doi = {10.1080/19490976.2025.2520412;WGROUP:STRING:PUBLICATION},
 journal = {Gut Microbes},
 number = {1}
}

Live microbiota therapies have shown promise in many gastrointestinal diseases, including in the prevention of recurrent Clostridioides difficile infections (rCDI); however, frameworks for their pharmacokinetic and pharmacodynamic analysis are not fully established. Fecal microbiota, live-jslm (RBL) is the first microbiota-based product approved by the US Food and Drug Administration for the prevention of rCDI and was superior to placebo in the PUNCH™ CD3 phase 3 clinical trial (NCT03244644). In this analysis, deep shotgun metagenomic sequencing was used to assess changes in gut microbiome compositions of participants and engraftment of bacterial clonal populations (i.e. strains) from RBL to recipients. Among RBL responders, gut microbiota shifted toward compositions that resembled healthy donors as early as 1 week after RBL administration; the resulting microbiota compositions included clonal populations that engrafted from RBL to recipients. Engraftment was higher in RBL responders compared with non-responders, and many clonally engrafted populations persisted for ≥ 6 months. Bacteroidia species were among the most effectively engrafted species from RBL. This study utilizes data from a large clinical trial to establish a method with high specificity for exploring clonal engraftment from microbiota-based treatments to facilitate future pharmacokinetic and pharmacodynamic analyses. Clinicaltrials Registration: NCT03244644.

@article{
 title = {Microbiome and resistome characterization of patients colonized with carbapenem-resistant Enterobacterales by long-read metagenomic next-generation sequencing of rectal swabs.},
 type = {article},
 year = {2025},
 pages = {dlaf152},
 volume = {7},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/40894237,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC12392892},
 month = {8},
 publisher = {Oxford University Press (OUP)},
 day = {2},
 id = {6654f840-5ed5-339e-b8c8-c57e5ae4a661},
 created = {2025-10-30T11:43:47.560Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:43:54.693Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {OBJECTIVES Evaluation of differences in the intestinal microbiome and resistome among high-risk patients (i.e. intensive care, oncology, transplant recipients) who are and are not colonized with carbapenem-resistant Enterobacterales (CRE). METHODS One hundred and twelve rectal swabs were obtained from 85 patients with known CRE colonization status and cohorted. Long-read metagenomic next-generation sequencing (mNGS) was performed on rectal swabs. Microbiome and resistome analysis were performed by assessing α-diversity, β-diversity, relative abundance assessment and linear discriminant analysis effect size (LEfSe), comparing patients colonized (CRE positive) and not colonized (CRE negative) with CRE. Longitudinal analysis of sequential swabs collected over multiple hospital encounters on a subset of patients was performed at the patient level. RESULTS The microbiomes of cohorts were similar when comparing α- and β-diversity measures and relative abundance. LEfSe analysis identified Gram-negative pathobionts enriched among CRE-positive samples and Gram-positive taxa enriched among CRE-negative samples. α-Diversity of the resistome differed at class, gene and allele levels. Relative abundance and LEfSe analysis demonstrated enrichment of genes conferring β-lactam resistance among CRE-positive patients; LEfSe also demonstrated enrichment of antimicrobial resistance genes to multiple antimicrobial classes. At the patient level, fluctuations in the microbiome and resistome among longitudinally collected swabs were associated with antibiotic exposure. CONCLUSIONS Differences between the microbiomes of CRE-positive- and CRE-negative-colonized patients at the cohort level were relatively muted, whereas statistically significant differences were observed among their resistomes. In patients followed longitudinally, shifts in microbiome and resistome composition were dramatic in between encounters and antibiotic exposures.},
 bibtype = {article},
 author = {Fissel, John A and Bergman, Yehudit and Campodónico, Victoria L and Walsh, Dana M and Fanelli, Brian and Arogyaswamy, Keshav and Kwon, Jennie H and Milstone, Aaron M and Tamma, Pranita D and Simner, Patricia J},
 doi = {10.1093/jacamr/dlaf152},
 journal = {JAC-antimicrobial resistance},
 number = {4}
}

OBJECTIVES Evaluation of differences in the intestinal microbiome and resistome among high-risk patients (i.e. intensive care, oncology, transplant recipients) who are and are not colonized with carbapenem-resistant Enterobacterales (CRE). METHODS One hundred and twelve rectal swabs were obtained from 85 patients with known CRE colonization status and cohorted. Long-read metagenomic next-generation sequencing (mNGS) was performed on rectal swabs. Microbiome and resistome analysis were performed by assessing α-diversity, β-diversity, relative abundance assessment and linear discriminant analysis effect size (LEfSe), comparing patients colonized (CRE positive) and not colonized (CRE negative) with CRE. Longitudinal analysis of sequential swabs collected over multiple hospital encounters on a subset of patients was performed at the patient level. RESULTS The microbiomes of cohorts were similar when comparing α- and β-diversity measures and relative abundance. LEfSe analysis identified Gram-negative pathobionts enriched among CRE-positive samples and Gram-positive taxa enriched among CRE-negative samples. α-Diversity of the resistome differed at class, gene and allele levels. Relative abundance and LEfSe analysis demonstrated enrichment of genes conferring β-lactam resistance among CRE-positive patients; LEfSe also demonstrated enrichment of antimicrobial resistance genes to multiple antimicrobial classes. At the patient level, fluctuations in the microbiome and resistome among longitudinally collected swabs were associated with antibiotic exposure. CONCLUSIONS Differences between the microbiomes of CRE-positive- and CRE-negative-colonized patients at the cohort level were relatively muted, whereas statistically significant differences were observed among their resistomes. In patients followed longitudinally, shifts in microbiome and resistome composition were dramatic in between encounters and antibiotic exposures.

@article{
 title = {Housing matters: Experimental variables shaping metabolism in obese mice},
 type = {article},
 year = {2025},
 keywords = {Animal models,High-fat diet,Housing conditions,Reproducibility,Sex differences,Thermoneutrality},
 volume = {98},
 month = {8},
 publisher = {Elsevier GmbH},
 day = {1},
 id = {ecb889b7-ac06-3b16-bf42-b412205ca89f},
 created = {2025-10-30T11:43:47.622Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:43:50.512Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Diet-induced obesity in mice is an important model for investigating host–diet interactions as well as dietary and pharmacological treatments of metabolic diseases. Experimental reproducibility is, however, a recurrent challenge. To determine key controllable experimental drivers of mouse metabolism, we distributed 338C57BL/6JBomTac mice (males and females) into six research units across two countries, divided them into a variety of housing conditions (i.e., diets, cage types, temperatures, group-housing vs. single-housing) and kept 26 reference mice at the vendor. We applied linear mixed models to rank the influence of each variable on metabolic phenotype (i.e., body weight gain, glucose intolerance, liver, and visceral adipose tissue weight). Group-housing was the most potent driver of metabolic dysfunction apart from sex and diet. Accordingly, single-housed mice exhibited reduced weight gain (∼50%), increased energy expenditure, and diminished respiratory exchange ratio concomitant with improved glucose tolerance (∼20%) compared to their group-housed counterparts. Our results may aid in clarifying the impact of experimental design and promote rational, transparent reporting to increase reproducibility.},
 bibtype = {article},
 author = {Choi, Béatrice So Yun and Holm, Jacob Bak and Brejnrod, Asker and Fjære, Even and Xia, Zhongkui and Allingbjerg, Marie Louise and Larsen, Ida Søgaard and Kristensen, David Møbjerg and Dall, Morten and Myrmel, Lene Secher and Koch, Janne and Danneskiold-Samsøe, Niels Banhos and Kalliokoski, Otto and Treebak, Jonas T. and Xiao, Liang and Hansen, Axel Kornerup and Sørensen, Helle and Madsen, Lise and Arumugam, Manimozhiyan and Kristiansen, Karsten and Jensen, Benjamin A.H.},
 doi = {10.1016/j.molmet.2025.102190},
 journal = {Molecular Metabolism}
}

Diet-induced obesity in mice is an important model for investigating host–diet interactions as well as dietary and pharmacological treatments of metabolic diseases. Experimental reproducibility is, however, a recurrent challenge. To determine key controllable experimental drivers of mouse metabolism, we distributed 338C57BL/6JBomTac mice (males and females) into six research units across two countries, divided them into a variety of housing conditions (i.e., diets, cage types, temperatures, group-housing vs. single-housing) and kept 26 reference mice at the vendor. We applied linear mixed models to rank the influence of each variable on metabolic phenotype (i.e., body weight gain, glucose intolerance, liver, and visceral adipose tissue weight). Group-housing was the most potent driver of metabolic dysfunction apart from sex and diet. Accordingly, single-housed mice exhibited reduced weight gain (∼50%), increased energy expenditure, and diminished respiratory exchange ratio concomitant with improved glucose tolerance (∼20%) compared to their group-housed counterparts. Our results may aid in clarifying the impact of experimental design and promote rational, transparent reporting to increase reproducibility.

@article{
 title = {Partially hydrolyzed, whey-based infant formula with six human milk oligosaccharides, B. infantis LMG11588, and B. lactis CNCM I-3446 is safe, well tolerated, and improves gut health: a staged analysis of a randomized trial.},
 type = {article},
 year = {2025},
 keywords = {bifidobacteria,gastrointestinal tolerance,growth,gut health,microbiota},
 pages = {1628847},
 volume = {12},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/40771223,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC12325064},
 publisher = {Frontiers Media SA},
 id = {86e15125-622d-35e9-9f68-8a1eff7bc966},
 created = {2025-10-30T11:43:47.624Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:43:50.825Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {BACKGROUND AND AIMS Gut health and microbiome development are closely linked in early life, with human milk oligosaccharides (HMOs) playing a key role. This study reports results through 4 months of age from a trial evaluating an infant formula containing a synbiotic blend of HMOs and probiotics, focusing on growth, gastrointestinal (GI) tolerance, and gut health biomarkers from birth to 15 months. MATERIALS AND METHODS Healthy infants aged ≤14 days were randomized to receive either the experimental formula (SYN; control formula supplemented with six HMOs and two probiotics [B. infantis, B. lactis]) or the control formula (CTRL; partially hydrolyzed 100% whey-based formula). A non-randomized breastfed (BF) group served as a reference. The primary endpoint was weight gain velocity in SYN vs. CTRL through 4 months of age. Secondary endpoints included fecal outcomes (abundance of bifidobacteria, immune and gut health markers), GI tolerance, and adverse events (AEs). RESULTS The full analysis set (FAS) included 313 infants (118 in SYN, 114 in CTRL, and 81 BF), while the per-protocol population (PP) included 227 infants (84 in SYN, 84 in CTRL, and 59 BF). Weight gain velocity through 4 months in the SYN group was non-inferior to that in the CTRL group in both FAS and PP analyses (both p < 0.0001). Parent-reported GI tolerance and stool patterns were similar between SYN and CTRL groups through 4 months. At 3 months, Bifidobacteria abundance was significantly higher in the SYN group compared to the CTRL group (p = 0.004). Fecal pH was lower in the SYN group than in the CTRL group (p = 0.018) and more closely resembled that of the BF group. Immune and gut health markers were similar between the SYN and BF groups. No significant differences in AEs were observed across groups. CONCLUSION The synbiotic-supplemented infant formula supported healthy, age-appropriate growth, good GI tolerance, and increased the abundance of beneficial bifidobacteria through 4 months of age. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov/study/NCT04962594.},
 bibtype = {article},
 author = {Picaud, Jean-Charles and Claris, Olivier and Gil-Campos, Mercedes and De La Cueva, Ignacio Salamanca and Cornette, Luc and Alliet, Philippe and Léké, André and Castanet, Mireille and Piloquet, Hugues and de Halleux, Virginie and Mitanchez, Delphine and Vandenplas, Yvan and Maton, Pierre and Jochum, Frank and Olbertz, Dirk and Policarpo, Sergio Negre and Lavalle, Luca and Fumero, Cecilia and Rodriguez-Garcia, Paula and Moll, Janne Marie and Silva-Zolezzi, Irma and Zemrani, Boutaina and Hays, Nicholas P and Sprenger, Norbert and Miranda-Mallea, Javier},
 doi = {10.3389/fnut.2025.1628847},
 journal = {Frontiers in nutrition}
}

BACKGROUND AND AIMS Gut health and microbiome development are closely linked in early life, with human milk oligosaccharides (HMOs) playing a key role. This study reports results through 4 months of age from a trial evaluating an infant formula containing a synbiotic blend of HMOs and probiotics, focusing on growth, gastrointestinal (GI) tolerance, and gut health biomarkers from birth to 15 months. MATERIALS AND METHODS Healthy infants aged ≤14 days were randomized to receive either the experimental formula (SYN; control formula supplemented with six HMOs and two probiotics [B. infantis, B. lactis]) or the control formula (CTRL; partially hydrolyzed 100% whey-based formula). A non-randomized breastfed (BF) group served as a reference. The primary endpoint was weight gain velocity in SYN vs. CTRL through 4 months of age. Secondary endpoints included fecal outcomes (abundance of bifidobacteria, immune and gut health markers), GI tolerance, and adverse events (AEs). RESULTS The full analysis set (FAS) included 313 infants (118 in SYN, 114 in CTRL, and 81 BF), while the per-protocol population (PP) included 227 infants (84 in SYN, 84 in CTRL, and 59 BF). Weight gain velocity through 4 months in the SYN group was non-inferior to that in the CTRL group in both FAS and PP analyses (both p < 0.0001). Parent-reported GI tolerance and stool patterns were similar between SYN and CTRL groups through 4 months. At 3 months, Bifidobacteria abundance was significantly higher in the SYN group compared to the CTRL group (p = 0.004). Fecal pH was lower in the SYN group than in the CTRL group (p = 0.018) and more closely resembled that of the BF group. Immune and gut health markers were similar between the SYN and BF groups. No significant differences in AEs were observed across groups. CONCLUSION The synbiotic-supplemented infant formula supported healthy, age-appropriate growth, good GI tolerance, and increased the abundance of beneficial bifidobacteria through 4 months of age. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov/study/NCT04962594.

@article{
 title = {The dynamics of the gut microbiota in prediabetes during a four-year follow-up among European patients—an IMI-DIRECT prospective study},
 type = {article},
 year = {2025},
 keywords = {Gut bacterial genetics,Gut bacterial microbiota,Gut viral microbiota,Insulin sensitivity,Long-term dynamics,Metabolism,Microbial functional pathways,Prediabetes},
 volume = {17},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {40315fc5-de75-34bf-9025-d83736db36e4},
 created = {2025-10-30T11:43:47.717Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:43:53.762Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Previous case–control studies have reported aberrations of the gut microbiota in individuals with prediabetes. The primary objective of the present study was to explore the dynamics of the gut microbiota of individuals with prediabetes over 4 years with a secondary aim of relating microbiota dynamics to temporal changes of metabolic phenotypes. Methods: The study included 486 European patients with prediabetes. Gut microbiota profiling was conducted using shotgun metagenomic sequencing and the same bioinformatics pipelines at study baseline and after 4 years. The same phenotyping protocols and core laboratory analyses were applied at the two timepoints. Phenotyping included anthropometrics and measurement of fasting plasma glucose and insulin levels, mean plasma glucose and insulin under an oral glucose tolerance test (OGTT), 2-h plasma glucose after an OGTT, oral glucose insulin sensitivity index, Matsuda insulin sensitivity index, body mass index, waist circumference, and systolic and diastolic blood pressure. Measures of the dynamics of bacterial microbiota were related to concomitant changes in markers of host metabolism. Results: Over 4 years, significant declines in richness were observed in gut bacterial and viral species and microbial pathways accompanied by significant changes in the relative abundance and the genetic composition of multiple bacterial species. Additionally, bacterial-viral interactions diminished over time. Despite the overall reduction in bacterial richness and microbial pathway richness, 80 dominant core bacterial species and 78 core microbial pathways were identified at both timepoints in 99% of the individuals, representing a resilient component of the gut microbiota. Over the same period, individuals with prediabetes exhibited a significant increase in glycemia and insulinemia alongside a significant decline in insulin sensitivity. Estimates of the gut bacterial microbiota dynamics were significantly correlated with temporal impairments in host metabolic health. Conclusions: In this 4-year prospective study of European patients with prediabetes, the gut microbiota exhibited major changes in taxonomic composition, bacterial species genetics, and microbial functional potentials, many of which paralleled an aggravation of host metabolism. Whether the temporal gut microbiota changes represent an adaptation to the progression of metabolic abnormalities or actively contribute to these in prediabetes cases remains unsettled. Trial registration: The Diabetes Research on Patient Stratification (DIRECT) study, an exploratory observational study initiated on October 15, 2012, was registered on ClinicalTrials.gov under the number NCT03814915.},
 bibtype = {article},
 author = {Lyu, Liwei and Fan, Yong and Vogt, Josef Korbinian and Clos-Garcia, Marc and Bonnefond, Amelie and Pedersen, Helle Krogh and Dutta, Avirup and Koivula, Robert and Sharma, Sapna and Allin, Kristine Højgaard and Brorsson, Caroline and Cederberg, Henna and Chabanova, Elizaveta and De Masi, Federico and Dermitzakis, Emmanouil and Elders, Petra J. and Blom, Marieke T. and Hollander, Monika and Eriksen, Rebeca and Forgie, Ian and Frost, Gary and Giordano, Giuseppe N. and Grallert, Harald and Haid, Mark and Hansen, Tue Haldor and Jablonka, Bernd and Kokkola, Tarja and Mahajan, Anubha and Mari, Andrea and McDonald, Timothy J. and Musholt, Petra B. and Pavo, Imre and Prehn, Cornelia and Ridderstråle, Martin and Ruetten, Hartmut and Hart, Leen M.‘t and Schwenk, Jochen M. and Stankevic, Evelina and Thomsen, Henrik S. and Vangipurapu, Jagadish and Vestergaard, Henrik and Viñuela, Ana and Walker, Mark and Hansen, Torben and Linneberg, Allan and Nielsen, Henrik Bjørn and Brunak, Søren and McCarthy, Mark I. and Froguel, Philippe and Adamski, Jerzy and Franks, Paul W. and Laakso, Marku and Beulens, Joline W.J. and Pearson, Ewan and Pedersen, Oluf},
 doi = {10.1186/s13073-025-01508-7},
 journal = {Genome Medicine},
 number = {1}
}

Background: Previous case–control studies have reported aberrations of the gut microbiota in individuals with prediabetes. The primary objective of the present study was to explore the dynamics of the gut microbiota of individuals with prediabetes over 4 years with a secondary aim of relating microbiota dynamics to temporal changes of metabolic phenotypes. Methods: The study included 486 European patients with prediabetes. Gut microbiota profiling was conducted using shotgun metagenomic sequencing and the same bioinformatics pipelines at study baseline and after 4 years. The same phenotyping protocols and core laboratory analyses were applied at the two timepoints. Phenotyping included anthropometrics and measurement of fasting plasma glucose and insulin levels, mean plasma glucose and insulin under an oral glucose tolerance test (OGTT), 2-h plasma glucose after an OGTT, oral glucose insulin sensitivity index, Matsuda insulin sensitivity index, body mass index, waist circumference, and systolic and diastolic blood pressure. Measures of the dynamics of bacterial microbiota were related to concomitant changes in markers of host metabolism. Results: Over 4 years, significant declines in richness were observed in gut bacterial and viral species and microbial pathways accompanied by significant changes in the relative abundance and the genetic composition of multiple bacterial species. Additionally, bacterial-viral interactions diminished over time. Despite the overall reduction in bacterial richness and microbial pathway richness, 80 dominant core bacterial species and 78 core microbial pathways were identified at both timepoints in 99% of the individuals, representing a resilient component of the gut microbiota. Over the same period, individuals with prediabetes exhibited a significant increase in glycemia and insulinemia alongside a significant decline in insulin sensitivity. Estimates of the gut bacterial microbiota dynamics were significantly correlated with temporal impairments in host metabolic health. Conclusions: In this 4-year prospective study of European patients with prediabetes, the gut microbiota exhibited major changes in taxonomic composition, bacterial species genetics, and microbial functional potentials, many of which paralleled an aggravation of host metabolism. Whether the temporal gut microbiota changes represent an adaptation to the progression of metabolic abnormalities or actively contribute to these in prediabetes cases remains unsettled. Trial registration: The Diabetes Research on Patient Stratification (DIRECT) study, an exploratory observational study initiated on October 15, 2012, was registered on ClinicalTrials.gov under the number NCT03814915.

@article{
 title = {Protozoal populations drive system-wide variation in the rumen microbiome},
 type = {article},
 year = {2025},
 volume = {16},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {186d3a2e-3f73-3351-98fa-1e49db6500f9},
 created = {2025-10-30T11:43:48.154Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:43:51.343Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {While rapid progress has been made to characterize the bacterial and archaeal populations of the rumen microbiome, insight into how they interact with keystone protozoal species remains elusive. Here, we reveal two distinct system-wide rumen community types (RCT-A and RCT-B) that are not strongly associated with host phenotype nor genotype but instead linked to protozoal community patterns. We leveraged a series of multi-omic datasets to show that the dominant Epidinium spp. in animals with RCT-B employ a plethora of fiber-degrading enzymes that present enriched Prevotella spp. a favorable carbon landscape to forage upon. Conversely, animals with RCT-A, dominated by genera Isotricha and Entodinium, harbor a more even distribution of fiber, protein, and amino acid metabolizers, reflected by higher detection of metabolites from both protozoal and bacterial activity. Our results indicate that microbiome variation across key protozoal and bacterial populations is interlinked, which should act as an important consideration for future development of microbiome-based technologies.},
 bibtype = {article},
 author = {Kobel, Carl M. and Leu, Andy and Vera-Ponce de León, Arturo and Øyås, Ove and Lai, Wanxin and Altshuler, Ianina and Hagen, Live H. and Wollenberg, Rasmus D. and Søndergaard, Mads T. and Bakshani, Cassie R. and Willats, William G.T. and Nicoll, Laura and McIlroy, Simon J. and Hvidsten, Torgeir R. and Schmidt, Oliver and Greening, Chris and Tyson, Gene W. and Roehe, Rainer and Aho, Velma T.E. and Pope, Phillip B.},
 doi = {10.1038/s41467-025-61302-2},
 journal = {Nature Communications },
 number = {1}
}

While rapid progress has been made to characterize the bacterial and archaeal populations of the rumen microbiome, insight into how they interact with keystone protozoal species remains elusive. Here, we reveal two distinct system-wide rumen community types (RCT-A and RCT-B) that are not strongly associated with host phenotype nor genotype but instead linked to protozoal community patterns. We leveraged a series of multi-omic datasets to show that the dominant Epidinium spp. in animals with RCT-B employ a plethora of fiber-degrading enzymes that present enriched Prevotella spp. a favorable carbon landscape to forage upon. Conversely, animals with RCT-A, dominated by genera Isotricha and Entodinium, harbor a more even distribution of fiber, protein, and amino acid metabolizers, reflected by higher detection of metabolites from both protozoal and bacterial activity. Our results indicate that microbiome variation across key protozoal and bacterial populations is interlinked, which should act as an important consideration for future development of microbiome-based technologies.

@article{
 title = {Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection},
 type = {article},
 year = {2025},
 keywords = {CDI,Clostridioides difficile,dysbiosis,engraftment,microbiome,microbiota-based product,pharmacodynamics,pharmacokinetics},
 volume = {17},
 publisher = {Taylor and Francis Ltd.},
 id = {8a9f1c14-b6f5-31fa-8bf8-0793eabdde24},
 created = {2025-10-30T11:48:01.152Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:48:01.152Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Live microbiota therapies have shown promise in many gastrointestinal diseases, including in the prevention of recurrent Clostridioides difficile infections (rCDI); however, frameworks for their pharmacokinetic and pharmacodynamic analysis are not fully established. Fecal microbiota, live-jslm (RBL) is the first microbiota-based product approved by the US Food and Drug Administration for the prevention of rCDI and was superior to placebo in the PUNCH™ CD3 phase 3 clinical trial (NCT03244644). In this analysis, deep shotgun metagenomic sequencing was used to assess changes in gut microbiome compositions of participants and engraftment of bacterial clonal populations (i.e. strains) from RBL to recipients. Among RBL responders, gut microbiota shifted toward compositions that resembled healthy donors as early as 1 week after RBL administration; the resulting microbiota compositions included clonal populations that engrafted from RBL to recipients. Engraftment was higher in RBL responders compared with non-responders, and many clonally engrafted populations persisted for ≥ 6 months. Bacteroidia species were among the most effectively engrafted species from RBL. This study utilizes data from a large clinical trial to establish a method with high specificity for exploring clonal engraftment from microbiota-based treatments to facilitate future pharmacokinetic and pharmacodynamic analyses. Clinicaltrials Registration: NCT03244644.},
 bibtype = {article},
 author = {Claypool, Josh and Lindved, Gustav and Myers, Pernille Neve and Ward, Tonya and Nielsen, Henrik Bjørn and Blount, Ken F.},
 doi = {10.1080/19490976.2025.2520412},
 journal = {Gut Microbes},
 number = {1}
}

Live microbiota therapies have shown promise in many gastrointestinal diseases, including in the prevention of recurrent Clostridioides difficile infections (rCDI); however, frameworks for their pharmacokinetic and pharmacodynamic analysis are not fully established. Fecal microbiota, live-jslm (RBL) is the first microbiota-based product approved by the US Food and Drug Administration for the prevention of rCDI and was superior to placebo in the PUNCH™ CD3 phase 3 clinical trial (NCT03244644). In this analysis, deep shotgun metagenomic sequencing was used to assess changes in gut microbiome compositions of participants and engraftment of bacterial clonal populations (i.e. strains) from RBL to recipients. Among RBL responders, gut microbiota shifted toward compositions that resembled healthy donors as early as 1 week after RBL administration; the resulting microbiota compositions included clonal populations that engrafted from RBL to recipients. Engraftment was higher in RBL responders compared with non-responders, and many clonally engrafted populations persisted for ≥ 6 months. Bacteroidia species were among the most effectively engrafted species from RBL. This study utilizes data from a large clinical trial to establish a method with high specificity for exploring clonal engraftment from microbiota-based treatments to facilitate future pharmacokinetic and pharmacodynamic analyses. Clinicaltrials Registration: NCT03244644.

@article{
 title = {Discovery of robust and highly specific microbiome signatures of non-alcoholic fatty liver disease},
 type = {article},
 year = {2025},
 keywords = {Gut microbiota,Machine learning,Metabolic diseases,Metabolomics,Microbial consortia,NAFLD,Network analysis},
 volume = {13},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {0b084754-b546-3b9c-b287-ac30ab991d0e},
 created = {2025-10-30T11:48:01.170Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:48:05.942Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) with a global prevalence of 30% is multifactorial and the involvement of gut bacteria has been recently proposed. However, finding robust bacterial signatures of NAFLD has been a great challenge, mainly due to its co-occurrence with other metabolic diseases. Results: Here, we collected public metagenomic data and integrated the taxonomy profiles with in silico generated community metabolic outputs, and detailed clinical data, of 1206 Chinese subjects w/wo metabolic diseases, including NAFLD (obese and lean), obesity, T2D, hypertension, and atherosclerosis. We identified highly specific microbiome signatures through building accurate machine learning models (accuracy = 0.845–0.917) for NAFLD with high portability (generalizable) and low prediction rate (specific) when applied to other metabolic diseases, as well as through a community approach involving differential co-abundance ecological networks. Moreover, using these signatures coupled with further mediation analysis and metabolic dependency modeling, we propose synergistic defined microbial consortia associated with NAFLD phenotype in overweight and lean individuals, respectively. Conclusion: Our study reveals robust and highly specific NAFLD signatures and offers a more realistic microbiome-therapeutics approach over individual species for this complex disease.},
 bibtype = {article},
 author = {Nychas, Emmanouil and Marfil-Sánchez, Andrea and Chen, Xiuqiang and Mirhakkak, Mohammad and Li, Huating and Jia, Weiping and Xu, Aimin and Nielsen, Henrik Bjørn and Nieuwdorp, Max and Loomba, Rohit and Ni, Yueqiong and Panagiotou, Gianni},
 doi = {10.1186/s40168-024-01990-y},
 journal = {Microbiome},
 number = {1}
}

Background: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) with a global prevalence of 30% is multifactorial and the involvement of gut bacteria has been recently proposed. However, finding robust bacterial signatures of NAFLD has been a great challenge, mainly due to its co-occurrence with other metabolic diseases. Results: Here, we collected public metagenomic data and integrated the taxonomy profiles with in silico generated community metabolic outputs, and detailed clinical data, of 1206 Chinese subjects w/wo metabolic diseases, including NAFLD (obese and lean), obesity, T2D, hypertension, and atherosclerosis. We identified highly specific microbiome signatures through building accurate machine learning models (accuracy = 0.845–0.917) for NAFLD with high portability (generalizable) and low prediction rate (specific) when applied to other metabolic diseases, as well as through a community approach involving differential co-abundance ecological networks. Moreover, using these signatures coupled with further mediation analysis and metabolic dependency modeling, we propose synergistic defined microbial consortia associated with NAFLD phenotype in overweight and lean individuals, respectively. Conclusion: Our study reveals robust and highly specific NAFLD signatures and offers a more realistic microbiome-therapeutics approach over individual species for this complex disease.

@article{
 title = {Shifts in Infant Skin Microbiome at 2 Months after Short-Term Emollient Use from Birth Are Associated with Reduced Prevalence of Atopic Dermatitis at 12 Months in a High-Risk Cohort},
 type = {article},
 year = {2025},
 keywords = {Atopic dermatitis,Barrier function,Emollient,FLG,Microbiome},
 pages = {2640-2643.e11},
 volume = {145},
 month = {10},
 publisher = {Elsevier B.V.},
 day = {1},
 id = {a4203c10-afac-3073-b64a-7de826b20f55},
 created = {2025-10-30T11:48:01.182Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:48:04.345Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Stamatas, Georgios N. and Insel, Richard and Sørensen, Nikolaj and Palleja, Albert and Moll, Janne Marie and Oddos, Thierry and Chaoimh, Carol Ní and O'B. Hourihane, Jonathan and Irvine, Alan D.},
 doi = {10.1016/j.jid.2025.03.017},
 journal = {Journal of Investigative Dermatology},
 number = {10}
}

@article{
 title = {Identification of Gut Microbiome Signatures and Metabolites Associated With Albuminuria in Type 2 Diabetes},
 type = {article},
 year = {2025},
 month = {8},
 publisher = {The Endocrine Society},
 day = {14},
 id = {475a5abd-2e31-388c-9990-8edfe4a07ee8},
 created = {2025-10-30T11:48:01.194Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:48:07.180Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {CONTEXT Type 2 diabetes is a growing global concern with serious complications, including kidney damage and cardiovascular morbidity and mortality. Monitoring albuminuria, which is associated with these complications, is crucial in optimal diabetes management. Gut microbiota composition has been suggested to impact albuminuria, but large studies with granular data are lacking. METHODS We investigated the relationship between 1002 gut microbial species, 1308 plasma metabolites and albuminuria in 752 participants with type 2 diabetes from the Swedish CArdioPulmonary BioImage Study. To determine the relative abundance of species, we employed deep shotgun metagenomic sequencing of fecal samples. Plasma metabolites were analyzed using mass spectrometry-based methods. RESULTS We identified three species that were associated with albuminuria, including Sellimonas intestinalis, Eggerthellales sp., Ellagibacter isourolithinifaciens. Two of these species were replicated in an independent pre-diabetic population (n=3,423) in SCAPIS. In total, 36 annotated metabolites were associated with the three albuminuria-signature species. Functional mapping of the signature species suggests a role in the regulation of the metabolites of imidazole propionate and trigonelline, which have previously been reported to play roles in the progression of albuminuria. CONCLUSIONS These findings provide additional evidence of the potential impact of microbial species and contribute to our understanding of the complex relationship between the gut microbiome, plasma metabolites, and albuminuria in individuals with diabetes.},
 bibtype = {article},
 author = {Lin, Yi-Ting and Sayols-Baixeras, Sergi and Graells, Tiscar and Dekkers, Koen F and Baldanzi, Gabriel and Nguyen, Diem and Larsson, Anders and Feldreich, Tobias Rudholm and Nielsen, Nynne and Eklund, Aron C and Holm, Jacob B and Nielsen, H Bjørn and Bergström, Göran and Smith, J Gustav and Malinovschi, Andrei and Engström, Gunnar and Orho-Melander, Marju and Fall, Tove and Ärnlöv, Johan},
 doi = {10.1210/clinem/dgaf453},
 journal = {The Journal of Clinical Endocrinology & Metabolism}
}

CONTEXT Type 2 diabetes is a growing global concern with serious complications, including kidney damage and cardiovascular morbidity and mortality. Monitoring albuminuria, which is associated with these complications, is crucial in optimal diabetes management. Gut microbiota composition has been suggested to impact albuminuria, but large studies with granular data are lacking. METHODS We investigated the relationship between 1002 gut microbial species, 1308 plasma metabolites and albuminuria in 752 participants with type 2 diabetes from the Swedish CArdioPulmonary BioImage Study. To determine the relative abundance of species, we employed deep shotgun metagenomic sequencing of fecal samples. Plasma metabolites were analyzed using mass spectrometry-based methods. RESULTS We identified three species that were associated with albuminuria, including Sellimonas intestinalis, Eggerthellales sp., Ellagibacter isourolithinifaciens. Two of these species were replicated in an independent pre-diabetic population (n=3,423) in SCAPIS. In total, 36 annotated metabolites were associated with the three albuminuria-signature species. Functional mapping of the signature species suggests a role in the regulation of the metabolites of imidazole propionate and trigonelline, which have previously been reported to play roles in the progression of albuminuria. CONCLUSIONS These findings provide additional evidence of the potential impact of microbial species and contribute to our understanding of the complex relationship between the gut microbiome, plasma metabolites, and albuminuria in individuals with diabetes.

@article{
 title = {Peptide abundance correlations in metaproteomics enhance taxonomic and functional analysis of the human gut microbiome},
 type = {article},
 year = {2025},
 volume = {11},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {b6a1ba03-9020-36eb-9221-f0abc7955b38},
 created = {2025-10-30T11:48:01.266Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:48:05.981Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Mass spectrometry (MS)-based proteomics is widely used for quantitative protein profiling and protein interaction studies. However, most current research focuses on single-species proteomics, while protein interactions within complex microbiomes, composed of hundreds of bacterial species, remain largely unexplored. In this study, we analyzed peptide abundance correlations within a metaproteomics dataset derived from in vitro cultured human gut microbiomes subjected to various drug treatments. Our analysis revealed that peptides from the same protein or taxon exhibited correlated abundance changes. By using t-SNE for visualization, we generated a peptide correlation map in which peptides from the same taxon formed distinct clusters. Furthermore, peptide abundance correlations enabled genome-level taxonomic assignments for a greater number of peptides. For instance, 1880 (48.9%) of the 3845 peptides initially assigned only to the family Bacteroidaceae could now be assigned to a specific genome. In species representative genome subsets, peptide correlation networks based on taxon-normalized peptide abundance (TNPA) linked functionally related peptides and provided insights into uncharacterized proteins. Altogether, our study demonstrates that analyzing peptide abundance correlations enhances both taxonomic and functional analyses in human gut metaproteomics research.},
 bibtype = {article},
 author = {Sun, Zhongzhi and Ning, Zhibin and Wu, Qing and Li, Leyuan and Doxey, Andrew C. and Figeys, Daniel},
 doi = {10.1038/s41522-025-00801-y},
 journal = {npj Biofilms and Microbiomes},
 number = {1}
}

Mass spectrometry (MS)-based proteomics is widely used for quantitative protein profiling and protein interaction studies. However, most current research focuses on single-species proteomics, while protein interactions within complex microbiomes, composed of hundreds of bacterial species, remain largely unexplored. In this study, we analyzed peptide abundance correlations within a metaproteomics dataset derived from in vitro cultured human gut microbiomes subjected to various drug treatments. Our analysis revealed that peptides from the same protein or taxon exhibited correlated abundance changes. By using t-SNE for visualization, we generated a peptide correlation map in which peptides from the same taxon formed distinct clusters. Furthermore, peptide abundance correlations enabled genome-level taxonomic assignments for a greater number of peptides. For instance, 1880 (48.9%) of the 3845 peptides initially assigned only to the family Bacteroidaceae could now be assigned to a specific genome. In species representative genome subsets, peptide correlation networks based on taxon-normalized peptide abundance (TNPA) linked functionally related peptides and provided insights into uncharacterized proteins. Altogether, our study demonstrates that analyzing peptide abundance correlations enhances both taxonomic and functional analyses in human gut metaproteomics research.

@article{
 title = {DNA reference reagents isolate biases in microbiome profiling: a global multi-lab study.},
 type = {article},
 year = {2025},
 keywords = {gut microbiome},
 pages = {e0046625},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/41104927},
 month = {10},
 day = {17},
 id = {093dcd92-a989-3127-afa3-b6f70d88fa4e},
 created = {2025-10-30T11:48:01.331Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T11:48:05.691Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {When profiling the human gut microbiome, technical biases introduced by analytical approaches impede translational research, reducing data reliability and study comparability. Here, through a global study involving 23 labs, we analyzed a wide range of sequencing and bioinformatic approaches for the taxonomic profiling of two well-defined DNA reference reagents (RRs) comprised of 20 common gut bacteria. Through both shotgun and 16S rRNA gene amplicon sequencing, we aimed to isolate sources of bias and understand their impact on microbiome profiling accuracy. Importantly, minimum quality criteria (MQC) were established and are used to evaluate profiling performance. We found that the variability of shotgun sequencing data sets was greater than that of 16S rRNA gene amplicon sequencing and isolated sources of bias in wet and dry lab steps, such as sequencing depth, primer and database choices, rarefaction, and 16S copy number adjustment. This study presents well-defined RRs and MQC to combat technical bias, paving the way for reliable and comparable microbiome research.IMPORTANCEThis benchmark paper highlights the true level of variability in microbiome data across the world and across sectors, underscoring the critical need for the use of WHO International DNA Gut Reference Reagents (RRs) to elevate the quality of data in microbiome research. This global study is the first of its kind, revealing the reality of the bias in the field, comprehensively testing methodologies used by leading laboratories across the world, but also providing avenues for workflow optimization, to accelerate innovation and translational research and move the field forward.},
 bibtype = {article},
 author = {Anwar, Saba and Lamaudiere, Matthew and Hassall, Jack and Dehinsilu, Jacob and Bhuller, Ravneet K and Hold, Georgina L and Vázquez-Campos, Xabier and Mahnert, Alexander and Moissl-Eichinger, Christine and Gallé, Birgit and Kainz, Gudrun and Pjevac, Petra and Hausmann, Bela and Schwarz, Jasmin and Kohl, Gudrun and Berry, David and Vancuren, Sarah J and Allen-Vercoe, Emma and Nielsen, Nynne and Sørensen, Nikolaj and Eklund, Aron and Nielsen, Henrik Bjørn and Riedel, René and Krause, Jannike Lea and Chang, Hyun-Dong and Park, Suenie and Song, Ho-Yeon and Seo, Hoonhee and Ul-Haq, Asad and Kim, Sukyung and Kwon, Yongbin and Park, Sunwha and Soberon, Xavier and Silva-Herzog, Eugenia and Verlouw, Joost A M and Arp, Pascal and Jhamai, Mila and Kraaij, Robert and Geelen, Anoecim R and Ducarmon, Quinten R and Smits, Wiep Klaas and Kuijper, Ed J and Zwittink, Romy D and van Best, Niels and Penders, John and Le, Giang and Driessen, Christel and Kool, Jolanda and Shetty, Sudarshan A and Fuentes, Susana and Demirci, Mehmet and Yigin, Akin and Whalley, Celina and Beggs, Andrew D and Quince, Christopher and James, Rob and Raguideau, Sebastien and Gordon, Martin and Mate, Ryan and Fritzsche, Martin and Danckert, Nathan P and Blanco, Jesus Miguens and Marchesi, Julian R and Rauch, Marcus and Williamson, R Anthony and Van't Wout, Angélique B and Kritz, Angelika and Rosecker, Stephan and Stevens, Richard and Laws, Lynette and Sayavedra, Lizbeth and Romano, Stefano and Telatin, Andrea and Baker, David and Narbad, Arjan and Servetas, Stephanie L and Kralj, Jason G and Forry, Samuel P and Hunter, Monique E and Dootz, Jennifer N and Jackson, Scott A and Mason, Christopher E and Butler, Daniel J and Mozsary, Christopher and Foox, Jonathan and Damle, Namita and Resh, Aidan and Busswitz, Amanda and Lenz, Peter and Sontag, Shane and Cross, Andrew and Sanchez, Christian and Guo, Mingsheng and Olson, Kayla and Smith, Eric A and La Reau, Alex J and Ward, Tonya and Kuersten, Scott and Hyde, Fred and Khrebtukova, Irina and Schroth, Gary and Rijpkema, Sjoerd and Amos, Gregory C A and Sergaki, Chrysi},
 editor = {Sangwan, Naseer},
 doi = {10.1128/msystems.00466-25},
 journal = {mSystems}
}

When profiling the human gut microbiome, technical biases introduced by analytical approaches impede translational research, reducing data reliability and study comparability. Here, through a global study involving 23 labs, we analyzed a wide range of sequencing and bioinformatic approaches for the taxonomic profiling of two well-defined DNA reference reagents (RRs) comprised of 20 common gut bacteria. Through both shotgun and 16S rRNA gene amplicon sequencing, we aimed to isolate sources of bias and understand their impact on microbiome profiling accuracy. Importantly, minimum quality criteria (MQC) were established and are used to evaluate profiling performance. We found that the variability of shotgun sequencing data sets was greater than that of 16S rRNA gene amplicon sequencing and isolated sources of bias in wet and dry lab steps, such as sequencing depth, primer and database choices, rarefaction, and 16S copy number adjustment. This study presents well-defined RRs and MQC to combat technical bias, paving the way for reliable and comparable microbiome research.IMPORTANCEThis benchmark paper highlights the true level of variability in microbiome data across the world and across sectors, underscoring the critical need for the use of WHO International DNA Gut Reference Reagents (RRs) to elevate the quality of data in microbiome research. This global study is the first of its kind, revealing the reality of the bias in the field, comprehensively testing methodologies used by leading laboratories across the world, but also providing avenues for workflow optimization, to accelerate innovation and translational research and move the field forward.

@article{
 title = {Meat intake in relation to composition and function of gut microbiota},
 type = {article},
 year = {2025},
 keywords = {Biomarkers,Meat,Metabolites,Microbiota},
 pages = {124-133},
 volume = {45},
 month = {2},
 publisher = {Churchill Livingstone},
 day = {1},
 id = {a16c7893-7470-3527-9fbf-a3eb1204d3fc},
 created = {2025-10-30T12:05:02.962Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:06.384Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Objective: Meat intake is suggested to affect gut microbiome composition and the risk of chronic diseases. We aimed to identify meat-associated gut microbiome features and their association with host factors. Design: Gut microbiota species were profiled by deep shotgun metagenomics sequencing in 9669 individuals. Intake of white meat, unprocessed red meat, and processed red meat was assessed using a food frequency questionnaire. The associations of meat intake with alpha-diversity and relative abundance of gut microbiota species were tested using linear regression models with adjustment for dietary fiber intake, body mass index, and other potential confounders. Meat-associated species were further assessed for association with enrichment of microbial gene function, meat-associated plasma metabolites, and clinical biomarkers. Results: Higher intake of processed red meat was associated with reduced alpha microbial diversity. White meat, unprocessed, and processed red meat intakes were associated with 36, 14, and 322 microbiota species, respectively. Species associated with processed red meat were enriched for bacterial pathways like amino acid degradation, while those negatively linked were enriched for pathways like homoacetogenesis. Furthermore, species positively associated with processed red meat were to a large extent associated with reduced trimethylamine N-oxide and glutamine levels but increased creatine and carnitine metabolites, fasting insulin and glucose, C-reactive protein, apolipoprotein A1, and triglyceride levels and higher blood pressure. Conclusion: This largest to date population-based study on meat and gut microbiota suggests that meat intake, particularly processed red meat, may modify the gut microbiota composition, functional capacity, and health-related biomarkers.},
 bibtype = {article},
 author = {Larsson, Susanna C. and Ericson, Ulrika and Dekkers, Koen F. and Arage, Getachew and Rašo, Luka Marko and Sayols-Baixeras, Sergi and Hammar, Ulf and Baldanzi, Gabriel and Nguyen, Diem and Nielsen, H. Bjørn and Holm, Jacob B. and Risérus, Ulf and Michaëlsson, Karl and Sundström, Johan and Smith, J. Gustav and Engström, Gunnar and Ärnlöv, Johan and Orho-Melander, Marju and Fall, Tove and Ahmad, Shafqat},
 doi = {10.1016/J.CLNU.2024.12.034},
 journal = {Clinical Nutrition}
}

Objective: Meat intake is suggested to affect gut microbiome composition and the risk of chronic diseases. We aimed to identify meat-associated gut microbiome features and their association with host factors. Design: Gut microbiota species were profiled by deep shotgun metagenomics sequencing in 9669 individuals. Intake of white meat, unprocessed red meat, and processed red meat was assessed using a food frequency questionnaire. The associations of meat intake with alpha-diversity and relative abundance of gut microbiota species were tested using linear regression models with adjustment for dietary fiber intake, body mass index, and other potential confounders. Meat-associated species were further assessed for association with enrichment of microbial gene function, meat-associated plasma metabolites, and clinical biomarkers. Results: Higher intake of processed red meat was associated with reduced alpha microbial diversity. White meat, unprocessed, and processed red meat intakes were associated with 36, 14, and 322 microbiota species, respectively. Species associated with processed red meat were enriched for bacterial pathways like amino acid degradation, while those negatively linked were enriched for pathways like homoacetogenesis. Furthermore, species positively associated with processed red meat were to a large extent associated with reduced trimethylamine N-oxide and glutamine levels but increased creatine and carnitine metabolites, fasting insulin and glucose, C-reactive protein, apolipoprotein A1, and triglyceride levels and higher blood pressure. Conclusion: This largest to date population-based study on meat and gut microbiota suggests that meat intake, particularly processed red meat, may modify the gut microbiota composition, functional capacity, and health-related biomarkers.

@article{
 title = {Protozoal populations drive system-wide variation in the rumen microbiome},
 type = {article},
 year = {2025},
 volume = {16},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {996ff065-aeaa-3a25-9bb1-ff9d8a609ef0},
 created = {2025-10-30T12:18:14.049Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:18:16.913Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {While rapid progress has been made to characterize the bacterial and archaeal populations of the rumen microbiome, insight into how they interact with keystone protozoal species remains elusive. Here, we reveal two distinct system-wide rumen community types (RCT-A and RCT-B) that are not strongly associated with host phenotype nor genotype but instead linked to protozoal community patterns. We leveraged a series of multi-omic datasets to show that the dominant Epidinium spp. in animals with RCT-B employ a plethora of fiber-degrading enzymes that present enriched Prevotella spp. a favorable carbon landscape to forage upon. Conversely, animals with RCT-A, dominated by genera Isotricha and Entodinium, harbor a more even distribution of fiber, protein, and amino acid metabolizers, reflected by higher detection of metabolites from both protozoal and bacterial activity. Our results indicate that microbiome variation across key protozoal and bacterial populations is interlinked, which should act as an important consideration for future development of microbiome-based technologies.},
 bibtype = {article},
 author = {Kobel, Carl M. and Leu, Andy and Vera-Ponce de León, Arturo and Øyås, Ove and Lai, Wanxin and Altshuler, Ianina and Hagen, Live H. and Wollenberg, Rasmus D. and Søndergaard, Mads T. and Bakshani, Cassie R. and Willats, William G.T. and Nicoll, Laura and McIlroy, Simon J. and Hvidsten, Torgeir R. and Schmidt, Oliver and Greening, Chris and Tyson, Gene W. and Roehe, Rainer and Aho, Velma T.E. and Pope, Phillip B.},
 doi = {10.1038/s41467-025-61302-2},
 journal = {Nature Communications },
 number = {1}
}

While rapid progress has been made to characterize the bacterial and archaeal populations of the rumen microbiome, insight into how they interact with keystone protozoal species remains elusive. Here, we reveal two distinct system-wide rumen community types (RCT-A and RCT-B) that are not strongly associated with host phenotype nor genotype but instead linked to protozoal community patterns. We leveraged a series of multi-omic datasets to show that the dominant Epidinium spp. in animals with RCT-B employ a plethora of fiber-degrading enzymes that present enriched Prevotella spp. a favorable carbon landscape to forage upon. Conversely, animals with RCT-A, dominated by genera Isotricha and Entodinium, harbor a more even distribution of fiber, protein, and amino acid metabolizers, reflected by higher detection of metabolites from both protozoal and bacterial activity. Our results indicate that microbiome variation across key protozoal and bacterial populations is interlinked, which should act as an important consideration for future development of microbiome-based technologies.

@article{
 title = { Dietary Supplementation with the Probiotic Bacillus velezensis BV379 Decreases Abdominal Bloating Without Perturbing the Commensal Gut Microbiota: A Randomized, Double-Blind, Placebo-Controlled Trial in Healthy Adults },
 type = {article},
 year = {2025},
 pages = {1-16},
 month = {9},
 publisher = {Informa UK Limited},
 day = {30},
 id = {5bf598ef-6bf2-3232-9eea-efd4c71f2384},
 created = {2025-10-30T12:26:00.894Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.894Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Garvey, Sean M. and Blonquist, Traci M. and Brutscher, Laura M. and Walsh, Dana M. and Kaden, Valerie N. and Beckman, Dawn B. and Zeng, Min and Bruno, Richard S. and Cook, Chad M. and Spears, Jessica L.},
 doi = {10.1080/27697061.2025.2563894},
 journal = {Journal of the American Nutrition Association}
}

@article{
 title = {Yanomami skin microbiome complexity challenges prevailing concepts of healthy skin},
 type = {article},
 year = {2025},
 volume = {16},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {f6522ee0-df88-3be5-bf41-b1db63ab687c},
 created = {2025-10-30T12:26:01.272Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:09.446Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The adult skin microbiome typically exhibits low microbial complexity, particularly on sebaceous sites, where lipophilic Cutibacterium and Malassezia spp. predominate. Current understanding of healthy skin microbiome is largely based on western, industrialized populations, with limited representation of diverse cultures and lifestyles. Here, we investigate the skin microbiome of a remote indigenous Yanomami community and reveal a complex microbial ecosystem comprising 115 previously unreported bacterial genomes. The Yanomami skin microbiome includes genera common to western populations alongside diverse environmental taxa that form multiplex interactions with the dominant eukaryote Malassezia globosa. Functional profiling indicates that this microbiome supports skin homeostasis by fortifying barrier integrity through lipid metabolism and acid production and mitigating oxidative stress. Longitudinal monitoring of western expeditioner’ skin demonstrates acquisition of the Yanomami microbiome following Amazonian immersion and its subsequent loss upon return to an industrialized setting. These findings reveal that diverse, environmentally enriched microbiota may confer skin benefits that are overlooked in current models of healthy skin.},
 bibtype = {article},
 author = {Durack, Juliana and Piceno, Yvette and Vuong, Hoang and Fanelli, Brian and Good, David A. and Hasan, Nur A. and Dadlani, Manoj and Weiss, Larry and Oh, Julia and Kostic, Aleksandar D. and Dawson, Thomas L. and Caballero-Arias, Hortensia and Colwell, Rita R.},
 doi = {10.1038/s41467-025-60131-7},
 journal = {Nature Communications },
 number = {1}
}

The adult skin microbiome typically exhibits low microbial complexity, particularly on sebaceous sites, where lipophilic Cutibacterium and Malassezia spp. predominate. Current understanding of healthy skin microbiome is largely based on western, industrialized populations, with limited representation of diverse cultures and lifestyles. Here, we investigate the skin microbiome of a remote indigenous Yanomami community and reveal a complex microbial ecosystem comprising 115 previously unreported bacterial genomes. The Yanomami skin microbiome includes genera common to western populations alongside diverse environmental taxa that form multiplex interactions with the dominant eukaryote Malassezia globosa. Functional profiling indicates that this microbiome supports skin homeostasis by fortifying barrier integrity through lipid metabolism and acid production and mitigating oxidative stress. Longitudinal monitoring of western expeditioner’ skin demonstrates acquisition of the Yanomami microbiome following Amazonian immersion and its subsequent loss upon return to an industrialized setting. These findings reveal that diverse, environmentally enriched microbiota may confer skin benefits that are overlooked in current models of healthy skin.

@article{
 title = {Engineered Receptor Capture Combined with Mass Spectrometry Enables High-Throughput Detection and Quantitation of SARS-CoV-2 Spike Protein.},
 type = {article},
 year = {2025},
 keywords = {ACE2,SARS-CoV2,detection,mass spectrometry,protein engineering,receptor capture,virus},
 pages = {747-755},
 volume = {5},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/40017752,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC11862925},
 month = {2},
 publisher = {American Chemical Society},
 day = {24},
 id = {61b175d9-ffef-3161-954a-9a7115622e27},
 created = {2025-10-30T12:28:33.451Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:37.790Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Mass spectrometry (MS) is a potentially powerful approach for the diagnostic detection of SARS-CoV-2 and other viruses. However, MS detection is compromised when viral antigens are present at low concentrations, especially in complex biological media. We hypothesized that viral receptors could be used for viral target capture to enable detection by MS under such conditions. This was tested using the extracellular domain of the SARS-CoV-2 receptor ACE2. To maximize recovery of the target protein, directed protein evolution was first used to increase the affinity of ACE2 for spike protein. This generated an evolved ACE2 with increased binding affinity for the spike protein receptor-binding domain (RBD). However, as with other affinity-enhanced evolved forms of ACE2, binding was sensitive to mutations in variant RBDs. As an alternative strategy to maximize capture, the native ACE2 extracellular domain was engineered for increased binding by the addition of an oligomerization scaffold to create pentameric ACE2. This bound extremely tightly to SARS-CoV-2 RBD, with an increase in apparent affinity of several thousand-fold over monomeric ACE2, and RBD retention of more than 8 h. Immobilization of multimeric ACE2 enabled quantitative enrichment of viral spike protein from saliva and increased the sensitivity of detection by MS. These data show that capture by engineered receptors combined with MS can be an effective, rapid method for detection and quantitation of target protein. A similar approach could be used for attachment proteins of other viruses or any target protein for which there are suitable receptors.},
 bibtype = {article},
 author = {Bate, Neil and Lane, Dan and Evans, Sian E and Salim, Farah and Allcock, Natalie S and Haigh, Richard and Sale, Julian E and Jones, Donald J L and Brindle, Nicholas P J},
 doi = {10.1021/jacsau.4c00980},
 journal = {JACS Au},
 number = {2}
}

Mass spectrometry (MS) is a potentially powerful approach for the diagnostic detection of SARS-CoV-2 and other viruses. However, MS detection is compromised when viral antigens are present at low concentrations, especially in complex biological media. We hypothesized that viral receptors could be used for viral target capture to enable detection by MS under such conditions. This was tested using the extracellular domain of the SARS-CoV-2 receptor ACE2. To maximize recovery of the target protein, directed protein evolution was first used to increase the affinity of ACE2 for spike protein. This generated an evolved ACE2 with increased binding affinity for the spike protein receptor-binding domain (RBD). However, as with other affinity-enhanced evolved forms of ACE2, binding was sensitive to mutations in variant RBDs. As an alternative strategy to maximize capture, the native ACE2 extracellular domain was engineered for increased binding by the addition of an oligomerization scaffold to create pentameric ACE2. This bound extremely tightly to SARS-CoV-2 RBD, with an increase in apparent affinity of several thousand-fold over monomeric ACE2, and RBD retention of more than 8 h. Immobilization of multimeric ACE2 enabled quantitative enrichment of viral spike protein from saliva and increased the sensitivity of detection by MS. These data show that capture by engineered receptors combined with MS can be an effective, rapid method for detection and quantitation of target protein. A similar approach could be used for attachment proteins of other viruses or any target protein for which there are suitable receptors.

@article{
 title = {Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators},
 type = {article},
 year = {2024},
 keywords = {GC-MS,MCF,lipidomics},
 pages = {2902-2916},
 volume = {119},
 websites = {https://pubmed.ncbi.nlm.nih.gov/37842925/},
 month = {12},
 publisher = {Cardiovasc Res},
 day = {1},
 id = {891351cb-5516-3889-9233-73430e98a7c2},
 created = {2025-07-07T13:25:48.145Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:30.928Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Aims Mutation of the PRDM16 gene causes human dilated and non-compaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with post-natal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored. Methods This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, and results monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN. Prdm16csp1/wt mice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice. Prdm16csp1/wt cardiac tissue of both sexes showed reductions in metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and the tricarboxylic acid cycle. Prdm16csp1/wt cardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. An accumulation of triacylglycerides exclusively in male Prdm16csp1/wt hearts suggests a sex-specific metabolic adaptation. Metabolic modelling using CARDIOKIN identified a reduction in fatty acid utilization in males as well as lower glucose utilization in female Prdm16csp1/wt cardiac tissue. On the level of transcripts and protein expression, Prdm16csp1/wt hearts demonstrate an up-regulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre-B-cell leukaemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional up-regulation was detected for Prdm16 itself, probably through an autoregulatory mechanism. Conclusions Monoallelic, global Prdm16 mutation diminishes cardiac performance in Prdm16csp1/wt mice. Metabolic alterations and transcriptional dysregulation in Prdm16csp1/wt affect cardiac tissue. Female Prdm16csp1/wt mice develop a more pronounced phenotype, indicating sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event in the PRDM16 associated cardiac pathology.},
 bibtype = {article},
 author = {Kühnisch, Jirko and Theisen, Simon and Dartsch, Josephine and Fritsche-Guenther, Raphaela and Kirchner, Marieluise and Obermayer, Benedikt and Bauer, Anna and Kahlert, Anne Karin and Rothe, Michael and Beule, Dieter and Heuser, Arnd and Mertins, Philipp and Kirwan, Jennifer A. and Berndt, Nikolaus and MacRae, Calum A. and Hubner, Norbert and Klaassen, Sabine},
 doi = {10.1093/CVR/CVAD154},
 journal = {Cardiovascular research},
 number = {18}
}

Aims Mutation of the PRDM16 gene causes human dilated and non-compaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with post-natal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored. Methods This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, and results monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN. Prdm16csp1/wt mice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice. Prdm16csp1/wt cardiac tissue of both sexes showed reductions in metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and the tricarboxylic acid cycle. Prdm16csp1/wt cardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. An accumulation of triacylglycerides exclusively in male Prdm16csp1/wt hearts suggests a sex-specific metabolic adaptation. Metabolic modelling using CARDIOKIN identified a reduction in fatty acid utilization in males as well as lower glucose utilization in female Prdm16csp1/wt cardiac tissue. On the level of transcripts and protein expression, Prdm16csp1/wt hearts demonstrate an up-regulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre-B-cell leukaemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional up-regulation was detected for Prdm16 itself, probably through an autoregulatory mechanism. Conclusions Monoallelic, global Prdm16 mutation diminishes cardiac performance in Prdm16csp1/wt mice. Metabolic alterations and transcriptional dysregulation in Prdm16csp1/wt affect cardiac tissue. Female Prdm16csp1/wt mice develop a more pronounced phenotype, indicating sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event in the PRDM16 associated cardiac pathology.

@article{
 title = {Profiling Plasma Extracellular Vesicle Metabotypes and miRNAs: An Unobserved Clue for Predicting Relapse in Patients with Early-Stage NSCLC},
 type = {article},
 year = {2024},
 pages = {3729},
 volume = {16},
 websites = {https://www.mdpi.com/2072-6694/16/22/3729},
 month = {11},
 day = {5},
 id = {fb38fc0f-53d5-3798-a18d-62d2ec29b63b},
 created = {2025-07-07T13:25:48.482Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:31.249Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {<p>Background and Objective: Lung cancer, the second most prevalent cancer globally, poses significant challenges in early detection and prognostic assessment. Despite advancements in targeted therapies and immunotherapy, the timely identification of relapse remains elusive. Blood-based liquid biopsy biomarkers, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating-free RNAs (cfRNAs), and extracellular vesicles (EVs)/exosomes, offer promise for non-invasive monitoring. Methods: We employ a comprehensive approach integrating miRNA/lncRNA/metabolomic datasets, following a mixed-methods content analysis, to identify candidate biomarkers in NSCLC. NSCLC-associated miRNA/gene/lncRNA associations were linked to in silico-derived molecular pathways. Results: For data validation, mass spectrometry-based untargeted metabolomics of plasma EVs highlighted miRNA/lncRNA/metabotypes, linking “glycerophospholipid metabolism” to lncRNA H19 and “alanine, aspartate and glutamate metabolism” to miR-29a-3p. Prognostic significance was established for miR-29a-3p, showing lower expression in NSCLC patients with disease progression compared to stable disease (p = 0.004). Kaplan–Meier survival analysis indicated that patients with miR-29a-3p under-expression had significantly shorter overall survival (OS) (p = 0.038). Despite the expression of lncRNA H19 in plasma EVs being undetected, its expression in plasma cfRNAs correlated significantly with disease progression (p = 0.035). Conclusions: Herein, we showcase the potential of plasma EV-derived miR-29a-3p as a prognostic biomarker and underscore the intricate interplay of miRNAs, lncRNAs, and metabolites in NSCLC biology. Our findings offer new insights and avenues for further exploration, contributing to the ongoing quest for effective biomarkers in early-stage NSCLC.</p>},
 bibtype = {article},
 author = {Bafiti, Vivi and Thanou, Eleni and Ouzounis, Sotiris and Kotsakis, Athanasios and Georgoulias, Vasilis and Lianidou, Evi and Katsila, Theodora and Markou, Athina},
 doi = {10.3390/cancers16223729},
 journal = {Cancers},
 number = {22}
}

Background and Objective: Lung cancer, the second most prevalent cancer globally, poses significant challenges in early detection and prognostic assessment. Despite advancements in targeted therapies and immunotherapy, the timely identification of relapse remains elusive. Blood-based liquid biopsy biomarkers, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating-free RNAs (cfRNAs), and extracellular vesicles (EVs)/exosomes, offer promise for non-invasive monitoring. Methods: We employ a comprehensive approach integrating miRNA/lncRNA/metabolomic datasets, following a mixed-methods content analysis, to identify candidate biomarkers in NSCLC. NSCLC-associated miRNA/gene/lncRNA associations were linked to in silico-derived molecular pathways. Results: For data validation, mass spectrometry-based untargeted metabolomics of plasma EVs highlighted miRNA/lncRNA/metabotypes, linking “glycerophospholipid metabolism” to lncRNA H19 and “alanine, aspartate and glutamate metabolism” to miR-29a-3p. Prognostic significance was established for miR-29a-3p, showing lower expression in NSCLC patients with disease progression compared to stable disease (p = 0.004). Kaplan–Meier survival analysis indicated that patients with miR-29a-3p under-expression had significantly shorter overall survival (OS) (p = 0.038). Despite the expression of lncRNA H19 in plasma EVs being undetected, its expression in plasma cfRNAs correlated significantly with disease progression (p = 0.035). Conclusions: Herein, we showcase the potential of plasma EV-derived miR-29a-3p as a prognostic biomarker and underscore the intricate interplay of miRNAs, lncRNAs, and metabolites in NSCLC biology. Our findings offer new insights and avenues for further exploration, contributing to the ongoing quest for effective biomarkers in early-stage NSCLC.

@article{
 title = {Gut microbiota drives colon cancer risk associated with diet: a comparative analysis of meat-based and pesco-vegetarian diets},
 type = {article},
 year = {2024},
 pages = {180},
 volume = {12},
 month = {12},
 day = {1},
 id = {ebfb7ffd-761b-3fd7-8f54-269d67bc7745},
 created = {2025-07-07T13:25:48.827Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:31.605Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {BACKGROUND: Colorectal cancer (CRC) risk is strongly affected by dietary habits with red and processed meat increasing risk, and foods rich in dietary fibres considered protective. Dietary habits also shape gut microbiota, but the role of the combination between diet, the gut microbiota, and the metabolite profile on CRC risk is still missing an unequivocal characterisation. METHODS: To investigate how gut microbiota affects diet-associated CRC risk, we fed Apc-mutated PIRC rats and azoxymethane (AOM)-induced rats the following diets: a high-risk red/processed meat-based diet (MBD), a normalised risk diet (MBD with α-tocopherol, MBDT), a low-risk pesco-vegetarian diet (PVD), and control diet. We then conducted faecal microbiota transplantation (FMT) from PIRC rats to germ-free rats treated with AOM and fed a standard diet for 3 months. We analysed multiple tumour markers and assessed the variations in the faecal microbiota using 16S rRNA gene sequencing together with targeted- and untargeted-metabolomics analyses. RESULTS: In both animal models, the PVD group exhibited significantly lower colon tumorigenesis than the MBD ones, consistent with various CRC biomarkers. Faecal microbiota and its metabolites also revealed significant diet-dependent profiles. Intriguingly, when faeces from PIRC rats fed these diets were transplanted into germ-free rats, those transplanted with MBD faeces developed a higher number of preneoplastic lesions together with distinctive diet-related bacterial and metabolic profiles. PVD determines a selection of nine taxonomic markers mainly belonging to Lachnospiraceae and Prevotellaceae families exclusively associated with at least two different animal models, and within these, four taxonomic markers were shared across all the three animal models. An inverse correlation between nonconjugated bile acids and bacterial genera mainly belonging to the Lachnospiraceae and Prevotellaceae families (representative of the PVD group) was present, suggesting a potential mechanism of action for the protective effect of these genera against CRC. CONCLUSIONS: These results highlight the protective effects of PVD while reaffirming the carcinogenic properties of MBD diets. In germ-free rats, FMT induced changes reminiscent of dietary effects, including heightened preneoplastic lesions in MBD rats and the transmission of specific diet-related bacterial and metabolic profiles. Importantly, to the best of our knowledge, this is the first study showing that diet-associated cancer risk can be transferred with faeces, establishing gut microbiota as a determinant of diet-associated CRC risk. Therefore, this study marks the pioneering demonstration of faecal transfer as a means of conveying diet-related cancer risk, firmly establishing the gut microbiota as a pivotal factor in diet-associated CRC susceptibility. Video Abstract.},
 bibtype = {article},
 author = {De Filippo, Carlotta and Chioccioli, Sofia and Meriggi, Niccolò and Troise, Antonio Dario and Vitali, Francesco and Mejia Monroy, Mariela and Özsezen, Serdar and Tortora, Katia and Balvay, Aurélie and Maudet, Claire and Naud, Nathalie and Fouché, Edwin and Buisson, Charline and Dupuy, Jacques and Bézirard, Valérie and Chevolleau, Sylvie and Tondereau, Valérie and Theodorou, Vassilia and Maslo, Claire and Aubry, Perrine and Etienne, Camille and Giovannelli, Lisa and Longo, Vincenzo and Scaloni, Andrea and Cavalieri, Duccio and Bouwman, Jildau and Pierre, Fabrice and Gérard, Philippe and Guéraud, Françoise and Caderni, Giovanna},
 doi = {10.1186/s40168-024-01900-2},
 journal = {Microbiome},
 number = {1}
}

BACKGROUND: Colorectal cancer (CRC) risk is strongly affected by dietary habits with red and processed meat increasing risk, and foods rich in dietary fibres considered protective. Dietary habits also shape gut microbiota, but the role of the combination between diet, the gut microbiota, and the metabolite profile on CRC risk is still missing an unequivocal characterisation. METHODS: To investigate how gut microbiota affects diet-associated CRC risk, we fed Apc-mutated PIRC rats and azoxymethane (AOM)-induced rats the following diets: a high-risk red/processed meat-based diet (MBD), a normalised risk diet (MBD with α-tocopherol, MBDT), a low-risk pesco-vegetarian diet (PVD), and control diet. We then conducted faecal microbiota transplantation (FMT) from PIRC rats to germ-free rats treated with AOM and fed a standard diet for 3 months. We analysed multiple tumour markers and assessed the variations in the faecal microbiota using 16S rRNA gene sequencing together with targeted- and untargeted-metabolomics analyses. RESULTS: In both animal models, the PVD group exhibited significantly lower colon tumorigenesis than the MBD ones, consistent with various CRC biomarkers. Faecal microbiota and its metabolites also revealed significant diet-dependent profiles. Intriguingly, when faeces from PIRC rats fed these diets were transplanted into germ-free rats, those transplanted with MBD faeces developed a higher number of preneoplastic lesions together with distinctive diet-related bacterial and metabolic profiles. PVD determines a selection of nine taxonomic markers mainly belonging to Lachnospiraceae and Prevotellaceae families exclusively associated with at least two different animal models, and within these, four taxonomic markers were shared across all the three animal models. An inverse correlation between nonconjugated bile acids and bacterial genera mainly belonging to the Lachnospiraceae and Prevotellaceae families (representative of the PVD group) was present, suggesting a potential mechanism of action for the protective effect of these genera against CRC. CONCLUSIONS: These results highlight the protective effects of PVD while reaffirming the carcinogenic properties of MBD diets. In germ-free rats, FMT induced changes reminiscent of dietary effects, including heightened preneoplastic lesions in MBD rats and the transmission of specific diet-related bacterial and metabolic profiles. Importantly, to the best of our knowledge, this is the first study showing that diet-associated cancer risk can be transferred with faeces, establishing gut microbiota as a determinant of diet-associated CRC risk. Therefore, this study marks the pioneering demonstration of faecal transfer as a means of conveying diet-related cancer risk, firmly establishing the gut microbiota as a pivotal factor in diet-associated CRC susceptibility. Video Abstract.

@article{
 title = {Sex specific gut-microbiota signatures of resilient and comorbid gut-brain phenotypes induced by early life stress},
 type = {article},
 year = {2024},
 keywords = {Early life stress,IBS,Microbiota,Psychiatric comorbidities,Resilience,Sex differences,Visceral pain},
 volume = {33},
 month = {11},
 publisher = {Elsevier Inc.},
 day = {1},
 id = {50bcfc55-5243-3d54-8f84-420c8c903020},
 created = {2025-07-07T13:25:49.174Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:31.959Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Alterations in gut-brain axis communication pathways and the gut microbiota ecosystem caused by early life stress have been extensively described as critical players in the pathophysiology of stress-induced disorders. However, the extent to which stress-induced gut microbiota alterations manifest in early life and contribute to the sex-specific susceptibility to distinct gut-brain phenotypes in adulthood has yet to be defined. Methods: Male and female Sprague-Dawley rat offspring underwent maternal separation (3h/day from postnatal day 2–12). Faecal samples were collected before weaning for gut microbiota 16S rRNA sequencing and metabolomic analysis. Visceral pain sensitivity and negative valence behaviours were assessed in adulthood using colorectal distension and the forced swim test respectively. Behavioural data were processed in a two-step cluster analysis to identify groupings within the dataset. Multi-omics analysis was carried out to investigate if the microbial signatures following early life stress were already defined according to the membership of the adult behavioural phenotypes. Results: Maternal separation resulted in increased visceral hypersensitivity while showing a trend for a sex-dependent increase in negative valence behaviour in adulthood. The cluster analysis revealed four clusters within the dataset representing distinct pathophysiological domains reminiscent of the behavioural consequences of early-life stress: 1. resilient, 2. pain, 3. immobile and 4. comorbid. The early life gut microbiota of each of these clusters show distinct alterations in terms of diversity, genus level differential abundance, and functional modules. Multi-omic integrations points towards a role for different metabolic pathways underlying each cluster-specific phenotype. Conclusion: Our study is the first to identify distinct phenotypes defined by susceptibility or resilience to gut-brain dysfunction induced by early life stress. The gut microbiota in early life shows sex-dependent alterations in each cluster that precede specific behavioural phenotypes in adulthood. Future research is warranted to determine the causal relationship between early-life stress-induced changes in the gut microbiota and to understand the trajectory leading to the manifestation of different behavioural phenotypes in adulthood.},
 bibtype = {article},
 author = {Wilmes, Lars and Caputi, Valentina and Bastiaanssen, Thomaz F.S. and Collins, James M. and Crispie, Fiona and Cotter, Paul D. and Dinan, Timothy G. and Cryan, John F. and Clarke, Gerard and O'Mahony, Siobhain M.},
 doi = {10.1016/j.ynstr.2024.100686},
 journal = {Neurobiology of Stress}
}

Background: Alterations in gut-brain axis communication pathways and the gut microbiota ecosystem caused by early life stress have been extensively described as critical players in the pathophysiology of stress-induced disorders. However, the extent to which stress-induced gut microbiota alterations manifest in early life and contribute to the sex-specific susceptibility to distinct gut-brain phenotypes in adulthood has yet to be defined. Methods: Male and female Sprague-Dawley rat offspring underwent maternal separation (3h/day from postnatal day 2–12). Faecal samples were collected before weaning for gut microbiota 16S rRNA sequencing and metabolomic analysis. Visceral pain sensitivity and negative valence behaviours were assessed in adulthood using colorectal distension and the forced swim test respectively. Behavioural data were processed in a two-step cluster analysis to identify groupings within the dataset. Multi-omics analysis was carried out to investigate if the microbial signatures following early life stress were already defined according to the membership of the adult behavioural phenotypes. Results: Maternal separation resulted in increased visceral hypersensitivity while showing a trend for a sex-dependent increase in negative valence behaviour in adulthood. The cluster analysis revealed four clusters within the dataset representing distinct pathophysiological domains reminiscent of the behavioural consequences of early-life stress: 1. resilient, 2. pain, 3. immobile and 4. comorbid. The early life gut microbiota of each of these clusters show distinct alterations in terms of diversity, genus level differential abundance, and functional modules. Multi-omic integrations points towards a role for different metabolic pathways underlying each cluster-specific phenotype. Conclusion: Our study is the first to identify distinct phenotypes defined by susceptibility or resilience to gut-brain dysfunction induced by early life stress. The gut microbiota in early life shows sex-dependent alterations in each cluster that precede specific behavioural phenotypes in adulthood. Future research is warranted to determine the causal relationship between early-life stress-induced changes in the gut microbiota and to understand the trajectory leading to the manifestation of different behavioural phenotypes in adulthood.

@article{
 title = {Gut microbiota regulates stress responsivity via the circadian system},
 type = {article},
 year = {2024},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/39504963},
 month = {11},
 publisher = {Cell Press},
 day = {5},
 id = {168b8714-6605-32f3-8747-3db9f170d928},
 created = {2025-07-07T13:25:49.491Z},
 accessed = {2025-01-07},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:49.491Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Stress and circadian systems are interconnected through the hypothalamic-pituitary-adrenal (HPA) axis to maintain responses to external stimuli. Yet, the mechanisms of how such signals are orchestrated remain unknown. Here, we uncover the gut microbiota as a regulator of HPA-axis rhythmicity. Microbial depletion disturbs the brain transcriptome and metabolome in stress-responding pathways in the hippocampus and amygdala across the day. This is coupled with a dysregulation of the circadian pacemaker in the brain that results in perturbed glucocorticoid rhythmicity. The resulting hyper-activation of the HPA axis at the sleep/wake transition drives time-of-day-specific impairments of the stress response and stress-sensitive behaviors. Finally, microbiota transplantation confirmed that diurnal oscillations of gut microbes underlie altered glucocorticoid secretion and that L. reuteri is a candidate strain for such effects. Our data offer compelling evidence that the microbiota regulates stress responsiveness in a circadian manner and is necessary to respond adaptively to stressors throughout the day.},
 bibtype = {article},
 author = {Tofani, Gabriel S S and Leigh, Sarah-Jane and Gheorghe, Cassandra E and Bastiaanssen, Thomaz F S and Wilmes, Lars and Sen, Paromita and Clarke, Gerard and Cryan, John F},
 doi = {10.1016/J.CMET.2024.10.003},
 journal = {Cell Metabolism}
}

Stress and circadian systems are interconnected through the hypothalamic-pituitary-adrenal (HPA) axis to maintain responses to external stimuli. Yet, the mechanisms of how such signals are orchestrated remain unknown. Here, we uncover the gut microbiota as a regulator of HPA-axis rhythmicity. Microbial depletion disturbs the brain transcriptome and metabolome in stress-responding pathways in the hippocampus and amygdala across the day. This is coupled with a dysregulation of the circadian pacemaker in the brain that results in perturbed glucocorticoid rhythmicity. The resulting hyper-activation of the HPA axis at the sleep/wake transition drives time-of-day-specific impairments of the stress response and stress-sensitive behaviors. Finally, microbiota transplantation confirmed that diurnal oscillations of gut microbes underlie altered glucocorticoid secretion and that L. reuteri is a candidate strain for such effects. Our data offer compelling evidence that the microbiota regulates stress responsiveness in a circadian manner and is necessary to respond adaptively to stressors throughout the day.

@article{
 title = {Maternal high-fat diet-induced microbiota changes are associated with alterations in embryonic brain metabolites and adolescent behaviour},
 type = {article},
 year = {2024},
 keywords = {Anxiety-like behaviour,Glutamate,Maternal obesity,Microbiota-gut-brain axis,Neurodevelopment},
 pages = {317-330},
 volume = {121},
 month = {10},
 publisher = {Academic Press},
 day = {1},
 id = {d74a3fca-49c0-3e29-ba79-c24357a56f18},
 created = {2025-07-07T13:25:49.808Z},
 accessed = {2025-01-07},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:32.343Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The developing central nervous system is highly sensitive to nutrient changes during the perinatal period, emphasising the potential impact of alterations of maternal diet on offspring brain development and behaviour. A growing body of research implicates the gut microbiota in neurodevelopment and behaviour. Maternal overweight and obesity during the perinatal period has been linked to changes in neurodevelopment, plasticity and affective disorders in the offspring, with implications for microbial signals from the maternal gut. Here we investigate the impact of maternal high-fat diet (mHFD)-induced changes in microbial signals on offspring brain development, and neuroimmune signals, and the enduring effects on behaviour into adolescence. We first demonstrate that maternal caecal microbiota composition at term pregnancy (embryonic day 18: E18) differs significantly in response to maternal diet. Moreover, mHFD resulted in the upregulation of microbial genes in the maternal intestinal tissue linked to alterations in quinolinic acid synthesis and elevated kynurenine levels in the maternal plasma, both neuronal plasticity mediators related to glutamate metabolism. Metabolomics of mHFD embryonic brains at E18 also detected molecules linked to glutamate-glutamine cycle, including glutamic acid, glutathione disulphide, and kynurenine. During adolescence, the mHFD offspring exhibited increased locomotor activity and anxiety-like behaviour in a sex-dependent manner, along with upregulation of glutamate-related genes compared to controls. Overall, our results demonstrate that maternal exposure to high-fat diet results in microbiota changes, behavioural imprinting, altered brain metabolism, and glutamate signalling during critical developmental windows during the perinatal period.},
 bibtype = {article},
 author = {Ratsika, Anna and Codagnone, Martin G. and Bastiaanssen, Thomaz F.S. and Hoffmann Sarda, Fabiana A. and Lynch, Caoimhe M.K. and Ventura-Silva, Ana Paula and Rosell-Cardona, Cristina and Caputi, Valentina and Stanton, Catherine and Fülling, Christine and Clarke, Gerard and Cryan, John F.},
 doi = {10.1016/J.BBI.2024.07.020},
 journal = {Brain, Behavior, and Immunity}
}

The developing central nervous system is highly sensitive to nutrient changes during the perinatal period, emphasising the potential impact of alterations of maternal diet on offspring brain development and behaviour. A growing body of research implicates the gut microbiota in neurodevelopment and behaviour. Maternal overweight and obesity during the perinatal period has been linked to changes in neurodevelopment, plasticity and affective disorders in the offspring, with implications for microbial signals from the maternal gut. Here we investigate the impact of maternal high-fat diet (mHFD)-induced changes in microbial signals on offspring brain development, and neuroimmune signals, and the enduring effects on behaviour into adolescence. We first demonstrate that maternal caecal microbiota composition at term pregnancy (embryonic day 18: E18) differs significantly in response to maternal diet. Moreover, mHFD resulted in the upregulation of microbial genes in the maternal intestinal tissue linked to alterations in quinolinic acid synthesis and elevated kynurenine levels in the maternal plasma, both neuronal plasticity mediators related to glutamate metabolism. Metabolomics of mHFD embryonic brains at E18 also detected molecules linked to glutamate-glutamine cycle, including glutamic acid, glutathione disulphide, and kynurenine. During adolescence, the mHFD offspring exhibited increased locomotor activity and anxiety-like behaviour in a sex-dependent manner, along with upregulation of glutamate-related genes compared to controls. Overall, our results demonstrate that maternal exposure to high-fat diet results in microbiota changes, behavioural imprinting, altered brain metabolism, and glutamate signalling during critical developmental windows during the perinatal period.

@article{
 title = {Exercise mitigates a gut microbiota-mediated reduction in adult hippocampal neurogenesis and associated behaviours in rats},
 type = {article},
 year = {2024},
 volume = {14},
 month = {12},
 publisher = {Springer Nature},
 day = {1},
 id = {21a049be-0330-3ebf-aec1-d0e3d4e6faee},
 created = {2025-07-07T13:25:50.147Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:32.677Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Lifestyle factors, especially exercise, impact the manifestation and progression of psychiatric and neurodegenerative disorders such as depression and Alzheimer’s disease, mediated by changes in hippocampal neuroplasticity. The beneficial effects of exercise may be due to its promotion of adult hippocampal neurogenesis (AHN). Gut microbiota has also been showed to be altered in a variety of brain disorders, and disturbances of the microbiota have resulted in alterations in brain and behaviour. However, whether exercise can counteract the negative effects of altered gut microbiota on brain function remains under explored. To this end, chronic disruption of the gut microbiota was achieved using an antibiotic cocktail in rats that were sedentary or allowed voluntary access to running wheels. Sedentary rats with disrupted microbiota displayed impaired performance in hippocampal neurogenesis-dependent tasks: the modified spontaneous location recognition task and the novelty suppressed feeding test. Performance in the elevated plus maze was also impaired due to antibiotics treatment. These behaviours, and an antibiotics-induced reduction in AHN were attenuated by voluntary exercise. The effects were independent of changes in the hippocampal metabolome but were paralleled by caecal metabolomic changes. Taken together these data highlight the importance of the gut microbiota in AHN-dependent behaviours and demonstrate the power of lifestyle factors such as voluntary exercise to attenuate these changes.},
 bibtype = {article},
 author = {Nicolas, Sarah and Dohm-Hansen, Sebastian and Lavelle, Aonghus and Bastiaanssen, Thomaz F.S. and English, Jane A. and Cryan, John F. and Nolan, Yvonne M.},
 doi = {10.1038/s41398-024-02904-0},
 journal = {Translational Psychiatry},
 number = {1}
}

Lifestyle factors, especially exercise, impact the manifestation and progression of psychiatric and neurodegenerative disorders such as depression and Alzheimer’s disease, mediated by changes in hippocampal neuroplasticity. The beneficial effects of exercise may be due to its promotion of adult hippocampal neurogenesis (AHN). Gut microbiota has also been showed to be altered in a variety of brain disorders, and disturbances of the microbiota have resulted in alterations in brain and behaviour. However, whether exercise can counteract the negative effects of altered gut microbiota on brain function remains under explored. To this end, chronic disruption of the gut microbiota was achieved using an antibiotic cocktail in rats that were sedentary or allowed voluntary access to running wheels. Sedentary rats with disrupted microbiota displayed impaired performance in hippocampal neurogenesis-dependent tasks: the modified spontaneous location recognition task and the novelty suppressed feeding test. Performance in the elevated plus maze was also impaired due to antibiotics treatment. These behaviours, and an antibiotics-induced reduction in AHN were attenuated by voluntary exercise. The effects were independent of changes in the hippocampal metabolome but were paralleled by caecal metabolomic changes. Taken together these data highlight the importance of the gut microbiota in AHN-dependent behaviours and demonstrate the power of lifestyle factors such as voluntary exercise to attenuate these changes.

@article{
 title = {The CSF lipid profile in patients with probable idiopathic normal pressure hydrocephalus differs from control but does not differ between shunt responders and non-responders},
 type = {article},
 year = {2024},
 keywords = {CSF,iNPH,lipidomics,mass spectrometry},
 volume = {6},
 publisher = {Oxford University Press},
 id = {da8b8691-5354-377e-a8ba-d1a27617c0e9},
 created = {2025-07-07T13:25:50.473Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:33.031Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Idiopathic normal pressure hydrocephalus is a common form of hydrocephalus in the elderly, characterized by enlarged ventricles combined with clinical symptoms presenting as gait impairment, urinary incontinence, and dementia. Idiopathic normal pressure hydrocephalus may be difficult to differentiate clinically from other neurodegenerative disorders, and up to 80% of cases may remain unrecognized and thus untreated. Consequently, there is a pressing demand for biomarkers that can confirm the diagnosis of idiopathic normal pressure hydrocephalus. In this exploratory study, CSF was sampled from the lumbar compartment of 21 control individuals and 19 probable idiopathic normal pressure hydrocephalus patients and analyzed by an untargeted mass spectroscopy-based platform to reveal a complete CSF lipid profile in these samples. Two hundred forty-four lipids from 17 lipid classes were detected in CSF. Various lipid classes, and select individual lipids, were reduced in the CSF obtained from patients with probable idiopathic normal pressure hydrocephalus, whereas a range of lipids belonging to the class of triacylglycerols was elevated. We detected no difference in the CSF lipid profile between probable idiopathic normal pressure hydrocephalus patients with and without clinical improvement following CSF shunting. In conclusion, the lipidomic profile of the CSF in patients with probable idiopathic normal pressure hydrocephalus, therefore, may serve as a sought after biomarker of the pathology, which may be employed to complement the clinical diagnosis.},
 bibtype = {article},
 author = {Toft-Bertelsen, Trine L. and Andreassen, Søren Norge and Simonsen, Anja Hviid and Hasselbalch, Steen Gregers and MacAulay, Nanna},
 doi = {10.1093/braincomms/fcae388},
 journal = {Brain Communications},
 number = {6}
}

Idiopathic normal pressure hydrocephalus is a common form of hydrocephalus in the elderly, characterized by enlarged ventricles combined with clinical symptoms presenting as gait impairment, urinary incontinence, and dementia. Idiopathic normal pressure hydrocephalus may be difficult to differentiate clinically from other neurodegenerative disorders, and up to 80% of cases may remain unrecognized and thus untreated. Consequently, there is a pressing demand for biomarkers that can confirm the diagnosis of idiopathic normal pressure hydrocephalus. In this exploratory study, CSF was sampled from the lumbar compartment of 21 control individuals and 19 probable idiopathic normal pressure hydrocephalus patients and analyzed by an untargeted mass spectroscopy-based platform to reveal a complete CSF lipid profile in these samples. Two hundred forty-four lipids from 17 lipid classes were detected in CSF. Various lipid classes, and select individual lipids, were reduced in the CSF obtained from patients with probable idiopathic normal pressure hydrocephalus, whereas a range of lipids belonging to the class of triacylglycerols was elevated. We detected no difference in the CSF lipid profile between probable idiopathic normal pressure hydrocephalus patients with and without clinical improvement following CSF shunting. In conclusion, the lipidomic profile of the CSF in patients with probable idiopathic normal pressure hydrocephalus, therefore, may serve as a sought after biomarker of the pathology, which may be employed to complement the clinical diagnosis.

@article{
 title = {Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid},
 type = {article},
 year = {2024},
 keywords = {CSF,biomarkers,lipidomics,mass spectrometry},
 volume = {14},
 month = {11},
 publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
 day = {1},
 id = {39f1e2dc-e7d1-31e2-8d1d-2dfcfaafa76a},
 created = {2025-07-07T13:25:50.861Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:33.370Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: The molecular composition of cerebrospinal fluid (CSF) is often used as a key indicator of biochemical alterations within distinct brain and spinal cord fluid compartments. The CSF protein content in lumbar CSF samples is widely employed as a biomarker matrix for diagnosing brain-related pathological conditions. CSF lipid profiles may serve as promising complementary diagnostics, but it remains unresolved if the lipid distribution is consistent along the neuroaxis. Methods: The lipid composition was determined with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in cisternal CSF obtained from healthy subjects undergoing preventive surgery of an unruptured aneurism (n = 11) and lumbar CSF obtained from individuals referred for the clinical evaluation of cognitive dysfunction but subsequently cleared and deemed healthy (n = 19). Results: We reveal discernible variations in lipid composition along the neuroaxis, with a higher overall lipid concentration in cisternal CSF, although with different relative distributions of the various lipid classes in the two compartments. The cisternal CSF contained elevated levels of most lipid classes, e.g., sphingomyelins, lysophosphatidylcholines, plasmenylphosphatidylcholines, phosphatidic acids, and triacylglycerols, whereas a few select lipids from the classes of fatty acids, phosphatidylcholines, amides and plasmenylphosphatidylethanolamines were, oppositely, elevated in the lumbar CSF pool. Conclusions: The distinct lipid distribution along the neuroaxis illustrates that the molecular constituents in these two CSF compartments are not uniform. These findings emphasize the necessity of establishing a lumbar lipid index for the accurate interpretation of the cranial CSF lipid profile.},
 bibtype = {article},
 author = {Toft-Bertelsen, Trine L. and Andreassen, Søren Norge and Norager, Nicolas H. and Simonsen, Anja Hviid and Hasselbalch, Steen Gregers and Juhler, Marianne and MacAulay, Nanna},
 doi = {10.3390/biom14111431},
 journal = {Biomolecules},
 number = {11}
}

Background: The molecular composition of cerebrospinal fluid (CSF) is often used as a key indicator of biochemical alterations within distinct brain and spinal cord fluid compartments. The CSF protein content in lumbar CSF samples is widely employed as a biomarker matrix for diagnosing brain-related pathological conditions. CSF lipid profiles may serve as promising complementary diagnostics, but it remains unresolved if the lipid distribution is consistent along the neuroaxis. Methods: The lipid composition was determined with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in cisternal CSF obtained from healthy subjects undergoing preventive surgery of an unruptured aneurism (n = 11) and lumbar CSF obtained from individuals referred for the clinical evaluation of cognitive dysfunction but subsequently cleared and deemed healthy (n = 19). Results: We reveal discernible variations in lipid composition along the neuroaxis, with a higher overall lipid concentration in cisternal CSF, although with different relative distributions of the various lipid classes in the two compartments. The cisternal CSF contained elevated levels of most lipid classes, e.g., sphingomyelins, lysophosphatidylcholines, plasmenylphosphatidylcholines, phosphatidic acids, and triacylglycerols, whereas a few select lipids from the classes of fatty acids, phosphatidylcholines, amides and plasmenylphosphatidylethanolamines were, oppositely, elevated in the lumbar CSF pool. Conclusions: The distinct lipid distribution along the neuroaxis illustrates that the molecular constituents in these two CSF compartments are not uniform. These findings emphasize the necessity of establishing a lumbar lipid index for the accurate interpretation of the cranial CSF lipid profile.

@article{
 title = {Altitude-dependent agro-ecologies impact the microbiome diversity of scavenging indigenous chicken in Ethiopia},
 type = {article},
 year = {2024},
 keywords = {Agro-ecology,Chicken,Ethiopia,Metagenomics,Microbiota,Poultry},
 volume = {12},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {ac9f111e-9936-3669-8dfd-c6763574f3a4},
 created = {2025-07-07T13:25:51.222Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:33.716Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Scavenging indigenous village chickens play a vital role in sub-Saharan Africa, sustaining the livelihood of millions of farmers. These chickens are exposed to vastly different environments and feeds compared to commercial chickens. In this study, we analysed the caecal microbiota of 243 Ethiopian village chickens living in different altitude-dependent agro-ecologies. Results: Differences in bacterial diversity were significantly correlated with differences in specific climate factors, topsoil characteristics, and supplemental diets provided by farmers. Microbiota clustered into three enterotypes, with one particularly enriched at high altitudes. We assembled 9977 taxonomically and functionally diverse metagenome-assembled genomes. The vast majority of these were not found in a dataset of previously published chicken microbes or in the Genome Taxonomy Database. Conclusions: The wide functional and taxonomic diversity of these microbes highlights their importance in the local adaptation of indigenous poultry, and the significant impacts of environmental factors on the microbiota argue for further discoveries in other agro-ecologies. EEwR8PKafK2-LVnkA2-YG-Video Abstract},
 bibtype = {article},
 author = {Glendinning, Laura and Jia, Xinzheng and Kebede, Adebabay and Oyola, Samuel O. and Park, Jong Eun and Park, Woncheoul and Assiri, Abdulwahab and Holm, Jacob Bak and Kristiansen, Karsten and Han, Jianlin and Hanotte, Olivier},
 doi = {10.1186/s40168-024-01847-4},
 journal = {Microbiome},
 number = {1}
}

Background: Scavenging indigenous village chickens play a vital role in sub-Saharan Africa, sustaining the livelihood of millions of farmers. These chickens are exposed to vastly different environments and feeds compared to commercial chickens. In this study, we analysed the caecal microbiota of 243 Ethiopian village chickens living in different altitude-dependent agro-ecologies. Results: Differences in bacterial diversity were significantly correlated with differences in specific climate factors, topsoil characteristics, and supplemental diets provided by farmers. Microbiota clustered into three enterotypes, with one particularly enriched at high altitudes. We assembled 9977 taxonomically and functionally diverse metagenome-assembled genomes. The vast majority of these were not found in a dataset of previously published chicken microbes or in the Genome Taxonomy Database. Conclusions: The wide functional and taxonomic diversity of these microbes highlights their importance in the local adaptation of indigenous poultry, and the significant impacts of environmental factors on the microbiota argue for further discoveries in other agro-ecologies. EEwR8PKafK2-LVnkA2-YG-Video Abstract

@article{
 title = {CHAMP delivers accurate taxonomic profiles of the prokaryotes, eukaryotes, and bacteriophages in the human microbiome},
 type = {article},
 year = {2024},
 keywords = {MAG,bacteriophages,benchmarking,human microbiome,metagenomics,taxonomic profiling},
 volume = {15},
 publisher = {Frontiers Media SA},
 id = {d144bbed-5dbc-3b32-8b2c-046ea048a2ca},
 created = {2025-10-30T12:05:02.939Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:05.819Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction: Accurate taxonomic profiling of the human microbiome composition is crucial for linking microbial species to health outcomes. Therefore, we created the Clinical Microbiomics Human Microbiome Profiler (CHAMP), a comprehensive tool designed for the profiling of prokaryotes, eukaryotes, and viruses across all body sites. Methods: CHAMP uses a reference database derived from 30,382 human microbiome samples, covering 6,567 prokaryotic and 244 eukaryotic species, as well as 64,003 viruses. We benchmarked CHAMP against established profiling tools (MetaPhlAn 4, Bracken 2, mOTUs 3, and Phanta) using a diverse set of in silico metagenomes and DNA mock communities. Results: CHAMP demonstrated unparalleled species recall, F1 score, and significantly reduced false positives compared to all other tools benchmarked. The false positive relative abundance (FPRA) for CHAMP was, on average, 50-fold lower than the second-best performing profiler. CHAMP also proved to be more robust than other tools at low sequencing depths, highlighting its application for low biomass samples. Discussion: Taken together, this establishes CHAMP as a best-in-class human microbiome profiler of prokaryotes, eukaryotes, and viruses in diverse and complex communities across low and high biomass samples. CHAMP profiling is offered as a service by Clinical Microbiomics A/S and is available for a fee at https://cosmosidhub.com.},
 bibtype = {article},
 author = {Pita, Sara and Myers, Pernille Neve and Johansen, Joachim and Russel, Jakob and Nielsen, Mads Cort and Eklund, Aron C. and Nielsen, Henrik Bjørn},
 doi = {10.3389/FMICB.2024.1425489},
 journal = {Frontiers in Microbiology}
}

Introduction: Accurate taxonomic profiling of the human microbiome composition is crucial for linking microbial species to health outcomes. Therefore, we created the Clinical Microbiomics Human Microbiome Profiler (CHAMP), a comprehensive tool designed for the profiling of prokaryotes, eukaryotes, and viruses across all body sites. Methods: CHAMP uses a reference database derived from 30,382 human microbiome samples, covering 6,567 prokaryotic and 244 eukaryotic species, as well as 64,003 viruses. We benchmarked CHAMP against established profiling tools (MetaPhlAn 4, Bracken 2, mOTUs 3, and Phanta) using a diverse set of in silico metagenomes and DNA mock communities. Results: CHAMP demonstrated unparalleled species recall, F1 score, and significantly reduced false positives compared to all other tools benchmarked. The false positive relative abundance (FPRA) for CHAMP was, on average, 50-fold lower than the second-best performing profiler. CHAMP also proved to be more robust than other tools at low sequencing depths, highlighting its application for low biomass samples. Discussion: Taken together, this establishes CHAMP as a best-in-class human microbiome profiler of prokaryotes, eukaryotes, and viruses in diverse and complex communities across low and high biomass samples. CHAMP profiling is offered as a service by Clinical Microbiomics A/S and is available for a fee at https://cosmosidhub.com.

@article{
 title = {The impact of daily supplementation with rhamnogalacturonan-I on the gut microbiota in healthy adults: A randomized controlled trial},
 type = {article},
 year = {2024},
 keywords = {Bifidobacterium,Common cold,Gut microbiota,Healthy adults,Pectin,Rhamnogalacturonan I},
 volume = {174},
 month = {5},
 publisher = {Elsevier Masson s.r.l.},
 day = {1},
 id = {d1effa8c-bc94-3014-a19a-36ce56ac1ac0},
 created = {2025-10-30T12:05:02.988Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:07.277Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Pectin and its derivatives have been shown to modulate immune signaling as well as gut microbiota in preclinical studies, which may constitute the mechanisms by which supplementation of specific pectic polysaccharides confers protection against viral respiratory infections. In a double-blind, placebo-controlled rhinovirus (RV16) challenge study, healthy volunteers were randomized to consume placebo (0.0 g/day) (N = 46), low-dose (0.3 g/day) (N = 49) or high-dose (1.5 g/day) (N = 51) of carrot derived rhamnogalacturonan-I (cRG-I) for eight weeks and they were subsequently challenged with RV-16. Here, the effect of 8-week cRG-I supplementation on the gut microbiota was studied. While the overall gut microbiota composition in the population was generally unaltered by this very low dose of fibre, the relative abundance of Bifidobacterium spp. (mainly B. adolescentis and B. longum) was significantly increased by both doses of cRG-1. Moreover, daily supplementation of cRG-I led to a dose-dependent reduction in inter- and intra-individual microbiota heterogeneity, suggesting a stabilizing effect on the gut microbiota. The severity of respiratory symptoms did not directly correlate with the cRG-I-induced microbial changes, but several dominant groups of the Ruminococcaceae family and microbiota richness were positively associated with a reduced and hence desired post-infection response. Thus, the present results on the modulation of the gut microbiota composition support the previously demonstrated immunomodulatory and protective effect of cRG-I during a common cold infection.},
 bibtype = {article},
 author = {Jian, Ching and Sorensen, Nikolaj and Lutter, René and Albers, Ruud and de Vos, Willem and Salonen, Anne and Mercenier, Annick},
 doi = {10.1016/J.BIOPHA.2024.116561},
 journal = {Biomedicine and Pharmacotherapy}
}

Pectin and its derivatives have been shown to modulate immune signaling as well as gut microbiota in preclinical studies, which may constitute the mechanisms by which supplementation of specific pectic polysaccharides confers protection against viral respiratory infections. In a double-blind, placebo-controlled rhinovirus (RV16) challenge study, healthy volunteers were randomized to consume placebo (0.0 g/day) (N = 46), low-dose (0.3 g/day) (N = 49) or high-dose (1.5 g/day) (N = 51) of carrot derived rhamnogalacturonan-I (cRG-I) for eight weeks and they were subsequently challenged with RV-16. Here, the effect of 8-week cRG-I supplementation on the gut microbiota was studied. While the overall gut microbiota composition in the population was generally unaltered by this very low dose of fibre, the relative abundance of Bifidobacterium spp. (mainly B. adolescentis and B. longum) was significantly increased by both doses of cRG-1. Moreover, daily supplementation of cRG-I led to a dose-dependent reduction in inter- and intra-individual microbiota heterogeneity, suggesting a stabilizing effect on the gut microbiota. The severity of respiratory symptoms did not directly correlate with the cRG-I-induced microbial changes, but several dominant groups of the Ruminococcaceae family and microbiota richness were positively associated with a reduced and hence desired post-infection response. Thus, the present results on the modulation of the gut microbiota composition support the previously demonstrated immunomodulatory and protective effect of cRG-I during a common cold infection.

@article{
 title = {Altitude-dependent agro-ecologies impact the microbiome diversity of scavenging indigenous chicken in Ethiopia},
 type = {article},
 year = {2024},
 keywords = {Agro-ecology,Chicken,Ethiopia,Metagenomics,Microbiota,Poultry},
 volume = {12},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {99d1fb90-39a4-35e2-8322-1214b2264acd},
 created = {2025-10-30T12:05:03.033Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:14.479Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Scavenging indigenous village chickens play a vital role in sub-Saharan Africa, sustaining the livelihood of millions of farmers. These chickens are exposed to vastly different environments and feeds compared to commercial chickens. In this study, we analysed the caecal microbiota of 243 Ethiopian village chickens living in different altitude-dependent agro-ecologies. Results: Differences in bacterial diversity were significantly correlated with differences in specific climate factors, topsoil characteristics, and supplemental diets provided by farmers. Microbiota clustered into three enterotypes, with one particularly enriched at high altitudes. We assembled 9977 taxonomically and functionally diverse metagenome-assembled genomes. The vast majority of these were not found in a dataset of previously published chicken microbes or in the Genome Taxonomy Database. Conclusions: The wide functional and taxonomic diversity of these microbes highlights their importance in the local adaptation of indigenous poultry, and the significant impacts of environmental factors on the microbiota argue for further discoveries in other agro-ecologies. EEwR8PKafK2-LVnkA2-YG-Video Abstract},
 bibtype = {article},
 author = {Glendinning, Laura and Jia, Xinzheng and Kebede, Adebabay and Oyola, Samuel O. and Park, Jong Eun and Park, Woncheoul and Assiri, Abdulwahab and Holm, Jacob Bak and Kristiansen, Karsten and Han, Jianlin and Hanotte, Olivier},
 doi = {10.1186/S40168-024-01847-4},
 journal = {Microbiome},
 number = {1}
}

Background: Scavenging indigenous village chickens play a vital role in sub-Saharan Africa, sustaining the livelihood of millions of farmers. These chickens are exposed to vastly different environments and feeds compared to commercial chickens. In this study, we analysed the caecal microbiota of 243 Ethiopian village chickens living in different altitude-dependent agro-ecologies. Results: Differences in bacterial diversity were significantly correlated with differences in specific climate factors, topsoil characteristics, and supplemental diets provided by farmers. Microbiota clustered into three enterotypes, with one particularly enriched at high altitudes. We assembled 9977 taxonomically and functionally diverse metagenome-assembled genomes. The vast majority of these were not found in a dataset of previously published chicken microbes or in the Genome Taxonomy Database. Conclusions: The wide functional and taxonomic diversity of these microbes highlights their importance in the local adaptation of indigenous poultry, and the significant impacts of environmental factors on the microbiota argue for further discoveries in other agro-ecologies. EEwR8PKafK2-LVnkA2-YG-Video Abstract

@article{
 title = {Characterization of the gut bacterial and viral microbiota in latent autoimmune diabetes in adults},
 type = {article},
 year = {2024},
 volume = {14},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {caab28c7-2a1e-361e-9ebc-b509d2b31c27},
 created = {2025-10-30T12:05:03.060Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:09.532Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by autoantibodies against insulin producing pancreatic beta cells and initial lack of need for insulin treatment. The aim of the present study was to investigate if individuals with LADA have an altered gut microbiota relative to non-diabetic control subjects, individuals with type 1 diabetes (T1D), and individuals with type 2 diabetes (T2D). Bacterial community profiling was performed with primers targeting the variable region 4 of the 16S rRNA gene and sequenced. Amplicon sequence variants (ASVs) were generated with DADA2 and annotated to the SILVA database. The gut virome was sequenced, using a viral particle enrichment and metagenomics approach, assembled, and quantified to describe the composition of the viral community. Comparison of the bacterial alpha- and beta-diversity measures revealed that the gut bacteriome of individuals with LADA resembled that of individuals with T2D. Yet, specific genera were found to differ in abundance in individuals with LADA compared with T1D and T2D, indicating that LADA has unique taxonomical features. The virome composition reflected the stability of the most dominant order Caudovirales and the families Siphoviridae, Podoviridae, and Inoviridae, and the dominant family Microviridae. Further studies are needed to confirm these findings.},
 bibtype = {article},
 author = {Poulsen, Casper S. and Hesse, Dan and Fernandes, Gabriel R. and Hansen, Tue H. and Kern, Timo and Linneberg, Allan and Van Espen, Lore and Jørgensen, Torben and Nielsen, Trine and Alibegovic, Amra C. and Matthijnssens, Jelle and Pedersen, Oluf and Vestergaard, Henrik and Hansen, Torben and Andersen, Mette K.},
 doi = {10.1038/S41598-024-58985-W},
 journal = {Scientific Reports},
 number = {1}
}

Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by autoantibodies against insulin producing pancreatic beta cells and initial lack of need for insulin treatment. The aim of the present study was to investigate if individuals with LADA have an altered gut microbiota relative to non-diabetic control subjects, individuals with type 1 diabetes (T1D), and individuals with type 2 diabetes (T2D). Bacterial community profiling was performed with primers targeting the variable region 4 of the 16S rRNA gene and sequenced. Amplicon sequence variants (ASVs) were generated with DADA2 and annotated to the SILVA database. The gut virome was sequenced, using a viral particle enrichment and metagenomics approach, assembled, and quantified to describe the composition of the viral community. Comparison of the bacterial alpha- and beta-diversity measures revealed that the gut bacteriome of individuals with LADA resembled that of individuals with T2D. Yet, specific genera were found to differ in abundance in individuals with LADA compared with T1D and T2D, indicating that LADA has unique taxonomical features. The virome composition reflected the stability of the most dominant order Caudovirales and the families Siphoviridae, Podoviridae, and Inoviridae, and the dominant family Microviridae. Further studies are needed to confirm these findings.

@article{
 title = {Gut microbiota composition is altered in postural orthostatic tachycardia syndrome and post-acute COVID-19 syndrome},
 type = {article},
 year = {2024},
 keywords = {Functional profiling,Gut microbiota,Long COVID,Post-acute COVID-19 syndrome (PACS),Postural orthostatic tachycardia syndrome (POTS),Taxonomic profiling},
 volume = {14},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {b1d8fc5a-c8c7-3206-85e3-687ceb948a0b},
 created = {2025-10-30T12:05:03.066Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:09.972Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Postural Orthostatic Tachycardia Syndrome (POTS) reflects an autonomic dysfunction, which can occur as a complication to COVID-19. Our aim was to examine gastrointestinal symptoms and gut microbiota composition in patients with POTS and post-acute COVID-19 syndrome (PACS), compared with controls. POTS patients (n = 27), PACS patients (n = 32) and controls (n = 39) delivered fecal samples and completed a 4-day food diary, irritable bowel syndrome-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). A total of 98 DNA aliquots were sequenced to an average depth of 28.3 million (M) read pairs (Illumina 2 × 150 PE) per sample. Diversity and taxonomic levels of the microbiome, as well as functional abundances were calculated for POTS and PACS groups, then compared with controls. There were several differences in taxonomic composition between POTS and controls, whereas only the abundance of Ascomycota and Firmicutes differed between PACS and controls. The clinical variables total IBS-SSS, fatigue, and bloating and flatulence significantly correlated with multiple individual taxa abundances, alpha diversity, and functional abundances. We conclude that POTS, and to a less extent PACS, are associated with differences in gut microbiota composition in diversity and at several taxonomic levels. Clinical symptoms are correlated with both alpha diversity and taxonomic and functional abundances.},
 bibtype = {article},
 author = {Hamrefors, Viktor and Kahn, Fredrik and Holmqvist, Madlene and Carlson, Katherine and Varjus, Roosa and Gudjonsson, Alexander and Fedorowski, Artur and Ohlsson, Bodil},
 doi = {10.1038/S41598-024-53784-9},
 journal = {Scientific Reports},
 number = {1}
}

Postural Orthostatic Tachycardia Syndrome (POTS) reflects an autonomic dysfunction, which can occur as a complication to COVID-19. Our aim was to examine gastrointestinal symptoms and gut microbiota composition in patients with POTS and post-acute COVID-19 syndrome (PACS), compared with controls. POTS patients (n = 27), PACS patients (n = 32) and controls (n = 39) delivered fecal samples and completed a 4-day food diary, irritable bowel syndrome-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). A total of 98 DNA aliquots were sequenced to an average depth of 28.3 million (M) read pairs (Illumina 2 × 150 PE) per sample. Diversity and taxonomic levels of the microbiome, as well as functional abundances were calculated for POTS and PACS groups, then compared with controls. There were several differences in taxonomic composition between POTS and controls, whereas only the abundance of Ascomycota and Firmicutes differed between PACS and controls. The clinical variables total IBS-SSS, fatigue, and bloating and flatulence significantly correlated with multiple individual taxa abundances, alpha diversity, and functional abundances. We conclude that POTS, and to a less extent PACS, are associated with differences in gut microbiota composition in diversity and at several taxonomic levels. Clinical symptoms are correlated with both alpha diversity and taxonomic and functional abundances.

@article{
 title = {Evaluation of inter- and intra-variability in gut health markers in healthy adults using an optimised faecal sampling and processing method},
 type = {article},
 year = {2024},
 volume = {14},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {d145f369-1f4c-3069-b92f-2129eb0f89eb},
 created = {2025-10-30T12:05:03.089Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:08.627Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Despite advances in gut health research, the variability of important gut markers within individuals over time remains underexplored. We investigated the intra-individual variation of various faecal gut health markers using an optimised processing protocol aimed at reducing variability. Faecal samples from ten healthy adults over three consecutive days demonstrated marker-specific intra-individual coefficients of variation (CV%), namely: stool consistency (16.5%), water content (5.7%), pH (3.9%), total SCFAs (17.2%), total BCFAs (27.4%), total bacteria and fungi copies (40.6% and 66.7%), calprotectin and myeloperoxidase (63.8% and 106.5%), and untargeted metabolites (on average 40%). For thirteen microbiota genera, including Bifidobacterium and Akkermansia, variability exceeded 30%, whereas microbiota diversity was less variable (Phylogenetic Diversity 3.3%, Inverse Simpson 17.2%). Mill-homogenisation of frozen faeces significantly reduced the replicates CV% for total SCFAs (20.4–7.5%) and total BCFAs (15.9–7.8%), and untargeted metabolites compared to faecal hammering only, without altering mean concentrations. Our results show the potential need for repeated sampling to accurately represent specific gut health markers. We also demonstrated the effectiveness of optimised preprocessing of human stool samples in reducing overall analytical variability.},
 bibtype = {article},
 author = {Kruger, Kirsten and Myeonghyun, Yoou and van der Wielen, Nicky and Kok, Dieuwertje E. and Hooiveld, Guido J. and Keshtkar, Shohreh and Diepeveen-de Bruin, Marlies and Balvers, Michiel G.J. and Grootte-Bromhaar, Mechteld and Mudde, Karin and Ly, Nhien T.H.N. and Vermeiren, Yannick and de Groot, Lisette C.P.G.M. and de Vos, Ric C.H. and Gonzales, Gerard Bryan and Steegenga, Wilma T. and van Trijp, Mara P.H.},
 doi = {10.1038/S41598-024-75477-Z},
 journal = {Scientific Reports},
 number = {1}
}

Despite advances in gut health research, the variability of important gut markers within individuals over time remains underexplored. We investigated the intra-individual variation of various faecal gut health markers using an optimised processing protocol aimed at reducing variability. Faecal samples from ten healthy adults over three consecutive days demonstrated marker-specific intra-individual coefficients of variation (CV%), namely: stool consistency (16.5%), water content (5.7%), pH (3.9%), total SCFAs (17.2%), total BCFAs (27.4%), total bacteria and fungi copies (40.6% and 66.7%), calprotectin and myeloperoxidase (63.8% and 106.5%), and untargeted metabolites (on average 40%). For thirteen microbiota genera, including Bifidobacterium and Akkermansia, variability exceeded 30%, whereas microbiota diversity was less variable (Phylogenetic Diversity 3.3%, Inverse Simpson 17.2%). Mill-homogenisation of frozen faeces significantly reduced the replicates CV% for total SCFAs (20.4–7.5%) and total BCFAs (15.9–7.8%), and untargeted metabolites compared to faecal hammering only, without altering mean concentrations. Our results show the potential need for repeated sampling to accurately represent specific gut health markers. We also demonstrated the effectiveness of optimised preprocessing of human stool samples in reducing overall analytical variability.

@article{
 title = {Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial},
 type = {article},
 year = {2024},
 volume = {15},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {76d45c05-7456-3315-b7fc-d036a839aab7},
 created = {2025-10-30T12:05:03.110Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:08.688Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI −1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = −0.482; 95% CI,−0.813, −0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.},
 bibtype = {article},
 author = {Ni Lochlainn, Mary and Bowyer, Ruth C.E. and Moll, Janne Marie and García, María Paz and Wadge, Samuel and Baleanu, Andrei Florin and Nessa, Ayrun and Sheedy, Alyce and Akdag, Gulsah and Hart, Deborah and Raffaele, Giulia and Seed, Paul T. and Murphy, Caroline and Harridge, Stephen D.R. and Welch, Ailsa A. and Greig, Carolyn and Whelan, Kevin and Steves, Claire J.},
 doi = {10.1038/S41467-024-46116-Y},
 journal = {Nature Communications },
 number = {1}
}

Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI −1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = −0.482; 95% CI,−0.813, −0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

@article{
 title = {Gulf War Illness Is Associated with Host Gut Microbiome Dysbiosis and Is Linked to Altered Species Abundance in Veterans from the BBRAIN Cohort.},
 type = {article},
 year = {2024},
 keywords = {Coprococcus,Eisenbergiella,Gulf War Illness,Lachnospiraceae,Multidimensional Fatigue Inventory,bacterial metabolism,bacteriome,chronic fatigue,veteran},
 volume = {21},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/39200711,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC11354743},
 month = {8},
 publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
 day = {21},
 id = {2b70cfdc-5e69-3802-ad62-9e115545ad6c},
 created = {2025-10-30T12:26:00.889Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:44.611Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Gulf War Illness (GWI) is a debilitating condition marked by chronic fatigue, cognitive problems, pain, and gastrointestinal (GI) complaints in veterans who were deployed to the 1990-1991 Gulf War. Fatigue, GI complaints, and other chronic symptoms continue to persist more than 30 years post-deployment. Several potential mechanisms for the persistent illness have been identified and our prior pilot study linked an altered gut microbiome with the disorder. This study further validates and builds on our prior preliminary findings of host gut microbiome dysbiosis in veterans with GWI. Using stool samples and Multidimensional Fatigue Inventory (MFI) data from 89 GW veteran participants (63 GWI cases and 26 controls) from the Boston biorepository, recruitment, and integrative network (BBRAIN) for Gulf War Illness, we found that the host gut bacterial signature of veterans with GWI showed significantly different Bray-Curtis beta diversity than control veterans. Specifically, a higher Firmicutes to Bacteroidetes ratio, decrease in Akkermansia sp., Bacteroides thetaiotamicron, Bacteroides fragilis, and Lachnospiraceae genera and increase in Blautia, Streptococcus, Klebsiella, and Clostridium genera, that are associated with gut, immune, and brain health, were shown. Further, using MaAsLin and Boruta algorithms, Coprococcus and Eisenbergiella were identified as important predictors of GWI with an area under the curve ROC predictive value of 74.8%. Higher self-reported MFI scores in veterans with GWI were also significantly associated with an altered gut bacterial diversity and species abundance of Lachnospiraceae and Blautia. These results suggest potential therapeutic targets for veterans with GWI that target the gut microbiome and specific symptoms of the illness.},
 bibtype = {article},
 author = {Trivedi, Ayushi and Bose, Dipro and Moffat, Kelly and Pearson, Elisabeth and Walsh, Dana and Cohen, Devra and Skupsky, Jonathan and Chao, Linda and Golier, Julia and Janulewicz, Patricia and Sullivan, Kimberly and Krengel, Maxine and Tuteja, Ashok and Klimas, Nancy and Chatterjee, Saurabh},
 doi = {10.3390/ijerph21081102},
 journal = {International journal of environmental research and public health},
 number = {8}
}

Gulf War Illness (GWI) is a debilitating condition marked by chronic fatigue, cognitive problems, pain, and gastrointestinal (GI) complaints in veterans who were deployed to the 1990-1991 Gulf War. Fatigue, GI complaints, and other chronic symptoms continue to persist more than 30 years post-deployment. Several potential mechanisms for the persistent illness have been identified and our prior pilot study linked an altered gut microbiome with the disorder. This study further validates and builds on our prior preliminary findings of host gut microbiome dysbiosis in veterans with GWI. Using stool samples and Multidimensional Fatigue Inventory (MFI) data from 89 GW veteran participants (63 GWI cases and 26 controls) from the Boston biorepository, recruitment, and integrative network (BBRAIN) for Gulf War Illness, we found that the host gut bacterial signature of veterans with GWI showed significantly different Bray-Curtis beta diversity than control veterans. Specifically, a higher Firmicutes to Bacteroidetes ratio, decrease in Akkermansia sp., Bacteroides thetaiotamicron, Bacteroides fragilis, and Lachnospiraceae genera and increase in Blautia, Streptococcus, Klebsiella, and Clostridium genera, that are associated with gut, immune, and brain health, were shown. Further, using MaAsLin and Boruta algorithms, Coprococcus and Eisenbergiella were identified as important predictors of GWI with an area under the curve ROC predictive value of 74.8%. Higher self-reported MFI scores in veterans with GWI were also significantly associated with an altered gut bacterial diversity and species abundance of Lachnospiraceae and Blautia. These results suggest potential therapeutic targets for veterans with GWI that target the gut microbiome and specific symptoms of the illness.

@article{
 title = {Microbial diversity, genomics, and phage–host interactions of cyanobacterial harmful algal blooms},
 type = {article},
 year = {2024},
 volume = {9},
 month = {7},
 publisher = {American Society for Microbiology},
 day = {23},
 id = {fba72359-59d9-3c85-aeaa-65f36d226184},
 created = {2025-10-30T12:26:00.934Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:11.810Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Cyanobacterial harmful algal blooms pose a significant threat to aquatic ecosystems and human health. Although physical and chemical conditions in aquatic systems that facilitate bloom development are well studied, there are fundamental gaps in the biological understanding of the microbial ecosystem that makes a cyanobacterial bloom. High-throughput sequencing was used to determine the drivers of cyanobacteria blooms in nature. Multiple functions and interactions important to consider in cyanobacterial bloom ecology were identified. The microbial biodiversity of blooms revealed microbial functions, genomic characteristics, and interactions between cyanobacterial populations that could be involved in bloom stability and more coherently define cyanobacteria blooms. Our results highlight the importance of considering cyanobacterial blooms as a microbial ecosystem to predict, prevent, and mitigate them.},
 bibtype = {article},
 author = {Krausfeldt, Lauren E. and Shmakova, Elizaveta and Lee, Hyo Won and Mazzei, Viviana and Loftin, Keith A. and Smith, Robert P. and Karwacki, Emily and Fortman, P. Eric and Rosen, Barry H. and Urakawa, Hidetoshi and Dadlani, Manoj and Colwell, Rita R. and Lopez, Jose V.},
 doi = {10.1128/msystems.00709-23},
 journal = {mSystems},
 number = {7}
}

Cyanobacterial harmful algal blooms pose a significant threat to aquatic ecosystems and human health. Although physical and chemical conditions in aquatic systems that facilitate bloom development are well studied, there are fundamental gaps in the biological understanding of the microbial ecosystem that makes a cyanobacterial bloom. High-throughput sequencing was used to determine the drivers of cyanobacteria blooms in nature. Multiple functions and interactions important to consider in cyanobacterial bloom ecology were identified. The microbial biodiversity of blooms revealed microbial functions, genomic characteristics, and interactions between cyanobacterial populations that could be involved in bloom stability and more coherently define cyanobacteria blooms. Our results highlight the importance of considering cyanobacterial blooms as a microbial ecosystem to predict, prevent, and mitigate them.

@article{
 title = {Whole-Genome Shotgun Metagenomic Sequencing Reveals Shifts in the Skin Microbiome and Bacteriophages of Psoriasis: An Extended Analysis of Published Data.},
 type = {article},
 year = {2024},
 keywords = {bacteria,fungi,metagenomics,microbiome,phage,psoriasis},
 pages = {98-107},
 volume = {9},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/39301212,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC11361494},
 month = {7},
 publisher = {SAGE Publications Ltd},
 day = {1},
 id = {77ed0651-0d23-3824-abec-623a53cce414},
 created = {2025-10-30T12:26:01.049Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.049Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {BACKGROUND Psoriasis is an immune-mediated cutaneous disease that may have shifts in the skin microbiome. Prior research on the skin microbiome in psoriasis has been limited to rRNA based approaches that lack resolution of taxonomic and functional level assessment. OBJECTIVE To further illuminate strain and sub-strain level analysis of psoriatic lesions using the CosmosID-HUB Microbiome pipeline. METHODS A previous study completed by Tett et al recruited patients with psoriasis who had skin microbiome samples taken from psoriatic plaques on the ear and the elbow as well as sites on the skin unaffected by psoriasis. They performed whole genome shotgun sequencing and made their dataset publicly available. We analyzed the dataset using the CosmosID-HUB Microbiome pipeline to evaluate the strain and sub-strain taxonomic analysis as well as functional gene profiling. RESULTS When analyzed with the CosmosID pipeline, both ear and elbow sites in affected areas had decreased alpha diversity compared to unaffected areas. There was an increased relative abundance of Staphylococcus and Corynebacteria at affected sites. We identified distinguishing species and strains of the yeast Malassezia, including M. restricta. that were significantly enriched in healthy elbow samples. Vitamin B12 production genes were not present in psoriatic skin whereas it was present in healthy samples, supporting the notion of relative vitamin B12 deficiency in psoriatic plaques. Phage analysis revealed a greater diversity of Staphylococcus-related phages in unaffected elbow samples. CONCLUSION A greater diversity of microbial strains and their functional roles identified in this study may help to tailor treatment for psoriasis.},
 bibtype = {article},
 author = {Nong, Yvonne and Walsh, Dana M and Maloh, Jessica and Dadlani, Manoj and Sivamani, Raja},
 doi = {10.1177/24755303241242357},
 journal = {Journal of psoriasis and psoriatic arthritis},
 number = {3}
}

BACKGROUND Psoriasis is an immune-mediated cutaneous disease that may have shifts in the skin microbiome. Prior research on the skin microbiome in psoriasis has been limited to rRNA based approaches that lack resolution of taxonomic and functional level assessment. OBJECTIVE To further illuminate strain and sub-strain level analysis of psoriatic lesions using the CosmosID-HUB Microbiome pipeline. METHODS A previous study completed by Tett et al recruited patients with psoriasis who had skin microbiome samples taken from psoriatic plaques on the ear and the elbow as well as sites on the skin unaffected by psoriasis. They performed whole genome shotgun sequencing and made their dataset publicly available. We analyzed the dataset using the CosmosID-HUB Microbiome pipeline to evaluate the strain and sub-strain taxonomic analysis as well as functional gene profiling. RESULTS When analyzed with the CosmosID pipeline, both ear and elbow sites in affected areas had decreased alpha diversity compared to unaffected areas. There was an increased relative abundance of Staphylococcus and Corynebacteria at affected sites. We identified distinguishing species and strains of the yeast Malassezia, including M. restricta. that were significantly enriched in healthy elbow samples. Vitamin B12 production genes were not present in psoriatic skin whereas it was present in healthy samples, supporting the notion of relative vitamin B12 deficiency in psoriatic plaques. Phage analysis revealed a greater diversity of Staphylococcus-related phages in unaffected elbow samples. CONCLUSION A greater diversity of microbial strains and their functional roles identified in this study may help to tailor treatment for psoriasis.

@article{
 title = {A Prospective Clinical Study to EvaluAte the AbiliTy of the CloudCath System to Detect Peritonitis During In-Home Peritoneal Dialysis (CATCH).},
 type = {article},
 year = {2024},
 keywords = {detection,peritoneal dialysis,peritonitis},
 pages = {929-940},
 volume = {9},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/38765568,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC11101817},
 month = {4},
 publisher = {Elsevier Inc.},
 day = {1},
 id = {f2321b53-2a0e-3732-81ef-5df591a7fc13},
 created = {2025-10-30T12:26:01.191Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:04.564Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {INTRODUCTION Peritonitis is the leading complication of peritoneal dialysis (PD). Patients are instructed to seek care promptly for signs (cloudy effluent) or symptoms (abdominal pain), and earlier treatment improves outcomes. The CloudCath Peritoneal Dialysis Drain Set Monitoring (CloudCath) system monitors turbidity in dialysis effluent and sends notifications of changes signaling possible peritonitis. METHODS We conducted this single-arm, open-label, multicenter study of CloudCath system use during PD. We deactivated system notifications to participants and investigators, who followed standard-of-care for peritonitis signs and symptoms. Effectiveness endpoints measured time between CloudCath system notifications and peritonitis events using International Society of Peritoneal Dialysis (ISPD) criteria. RESULTS Two hundred forty-three participants used the CloudCath system for 178.8 patient-years. Of 71 potential peritonitis events, 51 events (0.29 per patient-year) met ISPD white blood cell (WBC) count criteria. The system triggered notifications for 41 of 51 events (80.4%), with a median lead time of 2.6 days (10%-90% range, -1.0 to 15.7; P < 0.0001). Excluding 6 peritonitis events that occurred when the system was not in use, the system triggered notifications for 41 of 45 events (91.1%), with a median lead time of 3.0 days (10%-90% range, -0.5 to 18.8; P < 0.0001). Of the 0.78 notifications per patient-year, the majority were peritonitis events or nonperitonitis events such as exit site and tunnel infections or catheter/cycler issues. CONCLUSION The CloudCath system detected peritonitis events during PD several days earlier than the current standard-of-care and has the capacity to send notifications that could expedite peritonitis diagnosis and treatment.},
 bibtype = {article},
 author = {Mehrotra, Rajnish and Williamson, Don E and Betts, C Ross and Greco, Barbara A and Yu, Eric and El-Badry, Aly and Fisher, Brian and Mehoudar, Paul D and Briggs, Benjamin and Chertow, Glenn M},
 doi = {10.1016/j.ekir.2024.01.033},
 journal = {Kidney international reports},
 number = {4}
}

INTRODUCTION Peritonitis is the leading complication of peritoneal dialysis (PD). Patients are instructed to seek care promptly for signs (cloudy effluent) or symptoms (abdominal pain), and earlier treatment improves outcomes. The CloudCath Peritoneal Dialysis Drain Set Monitoring (CloudCath) system monitors turbidity in dialysis effluent and sends notifications of changes signaling possible peritonitis. METHODS We conducted this single-arm, open-label, multicenter study of CloudCath system use during PD. We deactivated system notifications to participants and investigators, who followed standard-of-care for peritonitis signs and symptoms. Effectiveness endpoints measured time between CloudCath system notifications and peritonitis events using International Society of Peritoneal Dialysis (ISPD) criteria. RESULTS Two hundred forty-three participants used the CloudCath system for 178.8 patient-years. Of 71 potential peritonitis events, 51 events (0.29 per patient-year) met ISPD white blood cell (WBC) count criteria. The system triggered notifications for 41 of 51 events (80.4%), with a median lead time of 2.6 days (10%-90% range, -1.0 to 15.7; P < 0.0001). Excluding 6 peritonitis events that occurred when the system was not in use, the system triggered notifications for 41 of 45 events (91.1%), with a median lead time of 3.0 days (10%-90% range, -0.5 to 18.8; P < 0.0001). Of the 0.78 notifications per patient-year, the majority were peritonitis events or nonperitonitis events such as exit site and tunnel infections or catheter/cycler issues. CONCLUSION The CloudCath system detected peritonitis events during PD several days earlier than the current standard-of-care and has the capacity to send notifications that could expedite peritonitis diagnosis and treatment.

@article{
 title = {Performance characteristics of a prototype dialysate turbidity monitoring system to detect peritonitis in patients receiving peritoneal dialysis},
 type = {article},
 year = {2024},
 keywords = {Peritoneal dialysis,peritonitis},
 pages = {419-425},
 volume = {44},
 month = {11},
 publisher = {SAGE Publications Inc.},
 day = {1},
 id = {67884f63-0136-3119-8fab-41a04ba0c14d},
 created = {2025-10-30T12:26:01.373Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.373Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: The risk of peritonitis has limited wider adoption of peritoneal dialysis (PD) in the United States. We developed a prototype bedside dialysate turbidity monitoring system, aiming to improve diagnostic accuracy relative to conventional approaches which depend on visual inspection and reporting of insensitive and non-specific symptoms. Methods: The prototype system was tested in a single-centre, proof-of-principle clinical study in patients receiving intermittent PD. We obtained multiple effluent dialysate samples from each consenting participant. We compared turbidity measurements with diagnostic criteria endorsed by the International Society of Peritoneal Dialysis (ISPD). Results: Overall, we analysed 983 specimens from 65 patients, including 105 samples from patients with peritonitis and 878 samples from patients without peritonitis. An operating point derived from a previous in vitro study yielded an unadjusted sensitivity and specificity of 95.2% and 91.5%, respectively. The majority of samples that did not meet ISPD diagnostic criteria were either cases detected before criteria were met or were related to active peritonitis treatment and resolution. Conclusion: This proof-of-principle study demonstrates the feasibility and diagnostic accuracy of a prototype dialysate turbidity monitoring system for peritonitis surveillance.},
 bibtype = {article},
 author = {Briggs, Benjamin and Garcia-Garcia, Guillermo and Ibarra-Hernandez, Margarita and Alcantar-Vallin, Luz and Walker, Gary and Yu, Eric and ElBadry, Aly and Fisher, Brian and Williamson, Don and Chertow, Glenn M.},
 doi = {10.1177/08968608231195532},
 journal = {Peritoneal Dialysis International},
 number = {6}
}

Background: The risk of peritonitis has limited wider adoption of peritoneal dialysis (PD) in the United States. We developed a prototype bedside dialysate turbidity monitoring system, aiming to improve diagnostic accuracy relative to conventional approaches which depend on visual inspection and reporting of insensitive and non-specific symptoms. Methods: The prototype system was tested in a single-centre, proof-of-principle clinical study in patients receiving intermittent PD. We obtained multiple effluent dialysate samples from each consenting participant. We compared turbidity measurements with diagnostic criteria endorsed by the International Society of Peritoneal Dialysis (ISPD). Results: Overall, we analysed 983 specimens from 65 patients, including 105 samples from patients with peritonitis and 878 samples from patients without peritonitis. An operating point derived from a previous in vitro study yielded an unadjusted sensitivity and specificity of 95.2% and 91.5%, respectively. The majority of samples that did not meet ISPD diagnostic criteria were either cases detected before criteria were met or were related to active peritonitis treatment and resolution. Conclusion: This proof-of-principle study demonstrates the feasibility and diagnostic accuracy of a prototype dialysate turbidity monitoring system for peritonitis surveillance.

@article{
 title = {Erratum: Correction for Alghofaili et al., "Host Stress Signals Stimulate Pneumococcal Transition from Colonization to Dissemination into the Lungs" (mBio (2021) 12 6 DOI: 10.1128/mBio.02569-21)},
 type = {article},
 year = {2024},
 pages = {e0287224},
 volume = {15},
 month = {12},
 day = {11},
 id = {51172faa-481d-3301-b6b7-466842e64655},
 created = {2025-10-30T12:28:33.452Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:33.452Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Alghofaili, Fayez and Najmuldeen, Hastyar and Kareem, Banaz O. and Shlla, Bushra and Fernandes, Vitor E. and Danielsen, Morten and Ketley, Julian M. and Freestone, Primrose and Yesilkaya, Hasan},
 doi = {10.1128/mbio.02872-24},
 journal = {mBio},
 number = {12}
}

@article{
 title = {Use of Nonhuman Sera as a Highly Cost-Effective Internal Standard for Quantitation of Multiple Human Proteins Using Species-Specific Tryptic Peptides: Applicability in Clinical LC-MS Analyses},
 type = {article},
 year = {2024},
 keywords = {bottom-up proteomics,cardiovascular risk markers,low cost,multiple reaction monitoring,quantitation,quantitative proteomics,selected reaction monitoring,surrogate standard,targeted proteomics},
 pages = {3052-3063},
 volume = {23},
 month = {8},
 publisher = {American Chemical Society},
 day = {2},
 id = {a32639af-b4e1-3aca-aa96-6df90a654d87},
 created = {2025-10-30T12:28:33.452Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:42.515Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Quantitation of proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is complex, with a multiplicity of options ranging from label-free techniques to chemically and metabolically labeling proteins. Increasingly, for clinically relevant analyses, stable isotope-labeled (SIL) internal standards (ISs) represent the “gold standard” for quantitation due to their similar physiochemical properties to the analyte, wide availability, and ability to multiplex to several peptides. However, the purchase of SIL-ISs is a resource-intensive step in terms of cost and time, particularly for screening putative biomarker panels of hundreds of proteins. We demonstrate an alternative strategy utilizing nonhuman sera as the IS for quantitation of multiple human proteins. We demonstrate the effectiveness of this strategy using two high abundance clinically relevant analytes, vitamin D binding protein [Gc globulin] (DBP) and albumin (ALB). We extend this to three putative risk markers for cardiovascular disease: plasma protease C1 inhibitor (SERPING1), annexin A1 (ANXA1), and protein kinase, DNA-activated catalytic subunit (PRKDC). The results show highly specific, reproducible, and linear measurement of the proteins of interest with comparable precision and accuracy to the gold standard SIL-IS technique. This approach may not be applicable to every protein, but for many proteins it can offer a cost-effective solution to LC-MS/MS protein quantitation.},
 bibtype = {article},
 author = {Williams, Geraldine and Couchman, Lewis and Taylor, David R. and Sandhu, Jatinderpal K. and Slingsby, Oliver C. and Ng, Leong L. and Moniz, Cajetan F. and Jones, Donald J.L. and Maxwell, Colleen B.},
 doi = {10.1021/acs.jproteome.3c00762},
 journal = {Journal of Proteome Research},
 number = {8}
}

Quantitation of proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is complex, with a multiplicity of options ranging from label-free techniques to chemically and metabolically labeling proteins. Increasingly, for clinically relevant analyses, stable isotope-labeled (SIL) internal standards (ISs) represent the “gold standard” for quantitation due to their similar physiochemical properties to the analyte, wide availability, and ability to multiplex to several peptides. However, the purchase of SIL-ISs is a resource-intensive step in terms of cost and time, particularly for screening putative biomarker panels of hundreds of proteins. We demonstrate an alternative strategy utilizing nonhuman sera as the IS for quantitation of multiple human proteins. We demonstrate the effectiveness of this strategy using two high abundance clinically relevant analytes, vitamin D binding protein [Gc globulin] (DBP) and albumin (ALB). We extend this to three putative risk markers for cardiovascular disease: plasma protease C1 inhibitor (SERPING1), annexin A1 (ANXA1), and protein kinase, DNA-activated catalytic subunit (PRKDC). The results show highly specific, reproducible, and linear measurement of the proteins of interest with comparable precision and accuracy to the gold standard SIL-IS technique. This approach may not be applicable to every protein, but for many proteins it can offer a cost-effective solution to LC-MS/MS protein quantitation.

@article{
 title = {A high throughput immuno-affinity mass spectrometry method for detection and quantitation of SARS-CoV-2 nucleoprotein in human saliva and its comparison with RT-PCR, RT-LAMP, and lateral flow rapid antigen test},
 type = {article},
 year = {2024},
 keywords = {RT-LAMP,RT-PCR,SARS-CoV-2,immuno-affinity,mass spectrometry,rapid antigen test},
 pages = {1206-1216},
 volume = {62},
 month = {5},
 publisher = {Walter de Gruyter GmbH},
 day = {1},
 id = {d8ed51d8-5a5f-3521-ad0d-c4cf2bbc61a8},
 created = {2025-10-30T12:28:33.464Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:37.023Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Objectives: Many reverse transcription polymerase chain reaction (RT-PCR) methods exist that can detect SARS-CoV-2 RNA in different matrices. RT-PCR is highly sensitive, although viral RNA may be detected long after active infection has taken place. SARS-CoV-2 proteins have shorter detection windows hence their detection might be more meaningful. Given salivary droplets represent a main source of transmission, we explored the detection of viral RNA and protein using four different detection platforms including SISCAPA peptide immunoaffinity liquid chromatography-mass spectrometry (SISCAPA-LC-MS) using polyclonal capture antibodies. Methods: The SISCAPA-LC MS method was compared to RT-PCR, RT-loop-mediated isothermal amplification (RT-LAMP), and a lateral flow rapid antigen test (RAT) for the detection of virus material in the drool saliva of 102 patients hospitalised after infection with SARS-CoV-2. Cycle thresholds (Ct) of RT-PCR (E gene) were compared to RT-LAMP time-to-positive (TTP) (NE and Orf1a genes), RAT optical densitometry measurements (test line/control line ratio) and to SISCAPA-LC-MS for measurements of viral protein. Results: SISCAPA-LC-MS showed low sensitivity (37.7 %) but high specificity (89.8 %). RAT showed lower sensitivity (24.5 %) and high specificity (100 %). RT-LAMP had high sensitivity (83.0 %) and specificity (100.0 %). At high initial viral RNA loads (<20 Ct), results obtained using SISCAPA-LC-MS correlated with RT-PCR (R2 0.57, p-value 0.002). Conclusions: Detection of SARS-CoV-2 nucleoprotein in saliva was less frequent than the detection of viral RNA. The SISCAPA-LC-MS method allowed processing of multiple samples in <150 min and was scalable, enabling high throughput.},
 bibtype = {article},
 author = {Lane, Dan and Allsopp, Rebecca and Holmes, Christopher W. and Slingsby, Oliver C. and Jukes-Jones, Rebekah and Bird, Paul and Anderson, N. Leigh and Razavi, Morteza and Yip, Richard and Pearson, Terry W. and Pope, Matt and Khunti, Kamlesh and Doykov, Ivan and Hällqvist, Jenny and Mills, Kevin and Skipp, Paul and Carling, Rachel and Ng, Leong and Shaw, Jacqui and Gupta, Pankaj and Jones, Donald J.L.},
 doi = {10.1515/cclm-2023-0243},
 journal = {Clinical Chemistry and Laboratory Medicine},
 number = {6}
}

Objectives: Many reverse transcription polymerase chain reaction (RT-PCR) methods exist that can detect SARS-CoV-2 RNA in different matrices. RT-PCR is highly sensitive, although viral RNA may be detected long after active infection has taken place. SARS-CoV-2 proteins have shorter detection windows hence their detection might be more meaningful. Given salivary droplets represent a main source of transmission, we explored the detection of viral RNA and protein using four different detection platforms including SISCAPA peptide immunoaffinity liquid chromatography-mass spectrometry (SISCAPA-LC-MS) using polyclonal capture antibodies. Methods: The SISCAPA-LC MS method was compared to RT-PCR, RT-loop-mediated isothermal amplification (RT-LAMP), and a lateral flow rapid antigen test (RAT) for the detection of virus material in the drool saliva of 102 patients hospitalised after infection with SARS-CoV-2. Cycle thresholds (Ct) of RT-PCR (E gene) were compared to RT-LAMP time-to-positive (TTP) (NE and Orf1a genes), RAT optical densitometry measurements (test line/control line ratio) and to SISCAPA-LC-MS for measurements of viral protein. Results: SISCAPA-LC-MS showed low sensitivity (37.7 %) but high specificity (89.8 %). RAT showed lower sensitivity (24.5 %) and high specificity (100 %). RT-LAMP had high sensitivity (83.0 %) and specificity (100.0 %). At high initial viral RNA loads (<20 Ct), results obtained using SISCAPA-LC-MS correlated with RT-PCR (R2 0.57, p-value 0.002). Conclusions: Detection of SARS-CoV-2 nucleoprotein in saliva was less frequent than the detection of viral RNA. The SISCAPA-LC-MS method allowed processing of multiple samples in <150 min and was scalable, enabling high throughput.

@article{
 title = {An optimised method to isotopically label pure synthetic peptides ‘in-house’ for absolute quantification in bottom-up proteomics},
 type = {article},
 year = {2024},
 volume = {38},
 month = {11},
 publisher = {John Wiley and Sons Ltd},
 day = {30},
 id = {ffe7b783-4d2d-36a3-8fc1-0fb6df305db8},
 created = {2025-10-30T12:28:34.375Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:34.375Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Rationale: Heavy-labelled internal standards increasingly represent the gold standard for absolute quantitation in mass spectrometry (MS)-based bottom-up proteomics. The biggest drawbacks of using these standards are that they have high costs and lengthy lead times. Methods: We describe an efficient, low-cost optimised method to enable ‘in-house’ heavy labelling of synthetic tryptic peptides for absolute quantification using tandem LC-MS/MS mass spectrometry. Our methodology uses 18O water in a trypsin-catalysed oxygen exchange reaction at the carboxyl terminus with the overall aim of reducing the costs and lead time associated with sourcing heavy standards from commercial vendors. Results: Step-by-step instructions are provided on how to execute this protocol with high-throughput adaptations utilising a 96-well plate and a liquid-handling robot. Detailed notes on experimental setup, tips for troubleshooting and suggested improvements to maximise labelling efficiencies are highlighted to achieve the best results. Under optimum conditions, labelling efficiencies of peptides can reach from 95% to 100%. Conclusions: The application of the ‘in-house’ labelled standards in generating calibration curves to quantify endogenous peptide concentrations is just as effective as using the synthetically sourced standards while also having great cost reduction implications as well as saving time spent waiting for peptides to arrive. The protocol is highly adaptable and can be customized to fit the specific setup of any laboratory, maximizing achievable labelling efficiencies.},
 bibtype = {article},
 author = {Bhakta, Nikita and Maxwell, Colleen B. and Atunde, Shimon and Sandhu, Jatinderpal K. and Slingsby, Oliver C. and Brady, Emer M. and Jones, Donald J.L. and Ng, Leong L.},
 doi = {10.1002/rcm.9892},
 journal = {Rapid Communications in Mass Spectrometry},
 number = {22}
}

Rationale: Heavy-labelled internal standards increasingly represent the gold standard for absolute quantitation in mass spectrometry (MS)-based bottom-up proteomics. The biggest drawbacks of using these standards are that they have high costs and lengthy lead times. Methods: We describe an efficient, low-cost optimised method to enable ‘in-house’ heavy labelling of synthetic tryptic peptides for absolute quantification using tandem LC-MS/MS mass spectrometry. Our methodology uses 18O water in a trypsin-catalysed oxygen exchange reaction at the carboxyl terminus with the overall aim of reducing the costs and lead time associated with sourcing heavy standards from commercial vendors. Results: Step-by-step instructions are provided on how to execute this protocol with high-throughput adaptations utilising a 96-well plate and a liquid-handling robot. Detailed notes on experimental setup, tips for troubleshooting and suggested improvements to maximise labelling efficiencies are highlighted to achieve the best results. Under optimum conditions, labelling efficiencies of peptides can reach from 95% to 100%. Conclusions: The application of the ‘in-house’ labelled standards in generating calibration curves to quantify endogenous peptide concentrations is just as effective as using the synthetically sourced standards while also having great cost reduction implications as well as saving time spent waiting for peptides to arrive. The protocol is highly adaptable and can be customized to fit the specific setup of any laboratory, maximizing achievable labelling efficiencies.

@article{
 title = {Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression},
 type = {article},
 year = {2023},
 keywords = {Animals,Diet,Gastrointestinal Microbiome* / genetics,High-Fat / adverse effects,Inbred C57BL,Liver / metabolism,MEDLINE,María Juárez-Fernández,Mice,Mitochondrial Proteins / metabolism,Molecular Chaperones / metabolism,NCBI,NIH,NLM,Naroa Goikoetxea-Usandizaga,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,Non-alcoholic Fatty Liver Disease* / metabolism,PMC10113004,PubMed Abstract,Research Support,Sonia Sánchez-Campos,doi:10.1002/hep.32705,pmid:35921199},
 pages = {1654-1669},
 volume = {77},
 websites = {https://pubmed.ncbi.nlm.nih.gov/35921199/},
 month = {5},
 publisher = {Hepatology},
 day = {1},
 id = {73fc4fff-f368-3560-bb2f-47e60905c1e1},
 created = {2025-07-07T13:25:41.308Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:41.308Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background and Aims: Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status. However, the underlying mechanism remains unclear. Herein, we hypothesized that enhanced mitochondrial activity might reshape a specific microbiota signature that, when transferred to germ-free (GF) mice, could delay NASH progression. Approach and Results: Wild-type and methylation-controlled J protein knockout (MCJ-KO) mice were fed for 6 weeks with either control or a choline-deficient, L-amino acid-defined, high-fat diet (CDA-HFD). One mouse of each group acted as a donor of cecal microbiota to GF mice, who also underwent the CDA-HFD model for 3 weeks. Hepatic injury, intestinal barrier, gut microbiome, and the associated fecal metabolome were then studied. Following 6 weeks of CDA-HFD, the absence of methylation-controlled J protein, an inhibitor of mitochondrial complex I activity, reduced hepatic injury and improved gut-liver axis in an aggressive NASH dietary model. This effect was transferred to GF mice through cecal microbiota transplantation. We suggest that the specific microbiota profile of MCJ-KO, characterized by an increase in the fecal relative abundance of Dorea and Oscillospira genera and a reduction in AF12, Allboaculum, and [Ruminococcus], exerted protective actions through enhancing short-chain fatty acids, nicotinamide adenine dinucleotide (NAD+) metabolism, and sirtuin activity, subsequently increasing fatty acid oxidation in GF mice. Importantly, we identified Dorea genus as one of the main modulators of this microbiota-dependent protective phenotype. Conclusions: Overall, we provide evidence for the relevance of mitochondria-microbiota interplay during NASH and that targeting it could be a valuable therapeutic approach.},
 bibtype = {article},
 author = {Juárez-Fernández, María and Goikoetxea-Usandizaga, Naroa and Porras, David and García-Mediavilla, María Victoria and Bravo, Miren and Serrano-Maciá, Marina and Simón, Jorge and Delgado, Teresa C. and Lachiondo-Ortega, Sofía and Martínez-Flórez, Susana and Lorenzo, Óscar and Rincón, Mercedes and Varela-Rey, Marta and Abecia, Leticia and Rodríguez, Héctor and Anguita, Juan and Nistal, Esther and Martínez-Chantar, María Luz and Sánchez-Campos, Sonia},
 doi = {10.1002/HEP.32705},
 journal = {Hepatology (Baltimore, Md.)},
 number = {5}
}

Background and Aims: Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status. However, the underlying mechanism remains unclear. Herein, we hypothesized that enhanced mitochondrial activity might reshape a specific microbiota signature that, when transferred to germ-free (GF) mice, could delay NASH progression. Approach and Results: Wild-type and methylation-controlled J protein knockout (MCJ-KO) mice were fed for 6 weeks with either control or a choline-deficient, L-amino acid-defined, high-fat diet (CDA-HFD). One mouse of each group acted as a donor of cecal microbiota to GF mice, who also underwent the CDA-HFD model for 3 weeks. Hepatic injury, intestinal barrier, gut microbiome, and the associated fecal metabolome were then studied. Following 6 weeks of CDA-HFD, the absence of methylation-controlled J protein, an inhibitor of mitochondrial complex I activity, reduced hepatic injury and improved gut-liver axis in an aggressive NASH dietary model. This effect was transferred to GF mice through cecal microbiota transplantation. We suggest that the specific microbiota profile of MCJ-KO, characterized by an increase in the fecal relative abundance of Dorea and Oscillospira genera and a reduction in AF12, Allboaculum, and [Ruminococcus], exerted protective actions through enhancing short-chain fatty acids, nicotinamide adenine dinucleotide (NAD+) metabolism, and sirtuin activity, subsequently increasing fatty acid oxidation in GF mice. Importantly, we identified Dorea genus as one of the main modulators of this microbiota-dependent protective phenotype. Conclusions: Overall, we provide evidence for the relevance of mitochondria-microbiota interplay during NASH and that targeting it could be a valuable therapeutic approach.

@article{
 title = {Co-fermentation of non-Saccharomyces yeasts with Lactiplantibacillus plantarum FST 1.7 for the production of non-alcoholic beer},
 type = {article},
 year = {2023},
 keywords = {Fermentate,MCF},
 pages = {167-181},
 volume = {249},
 websites = {https://link.springer.com/article/10.1007/s00217-022-04142-4},
 month = {1},
 publisher = {Springer Science and Business Media Deutschland GmbH},
 day = {1},
 id = {f28081cd-be9c-3f3c-875c-c03aec722348},
 created = {2025-07-07T13:25:41.730Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:25.249Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The non-alcoholic beer (NAB) sector has experienced steady growth in recent years, with breweries continuously seeking new ways to fulfil consumer demands. NAB can be produced by limited fermentation of non-Saccharomyces yeasts; however, beer produced in this manner is often critiqued for its sweet taste and wort-like off-flavours due to high levels of residual sugars and lack of flavour metabolites. The use of Lactobacillus in limited co-fermentation with non-Saccharomyces yeasts is a novel approach to produce NABs with varying flavour and aroma characteristics. In this study, lab-scale fermentations of Lachancea fermentati KBI 12.1 and Cyberlindnera subsufficiens C6.1 with Lactiplantibacillus plantarum FST 1.7 were performed and compared to a brewer’s yeast, Saccharomyces cerevisiae WLP001. Fermentations were monitored for pH, TTA, extract reduction, alcohol production, and microbial cell count. The final beers were analysed for sugar and organic acid concentration, free amino nitrogen content (FAN), glycerol, and levels of volatile metabolites. The inability of the non-Saccharomyces yeasts to utilise maltotriose as an energy source resulted in extended fermentation times compared to S. cerevisiae WLP001. Co-fermentation of yeasts with lactic acid bacteria (LAB) resulted in a decreased pH, higher TTA and increased levels of lactic acid in the final beers. The overall acceptability of the NABs produced by co-fermentation was higher than or similar to that of the beers fermented with the yeasts alone, indicating that LAB fermentation did not negatively impact the sensory attributes of the beer. C. subsufficiens C6.1 and L. plantarum FST 1.7 NAB was characterised as fruity tasting with the significantly higher ester concentrations masking the wort-like flavours resulting from limited fermentation. NAB produced with L. fermentati KBI12.1 and L. plantarum FST1.7 had decreased levels of the undesirable volatile compound diacetyl and was described as ‘fruity’ and ‘acidic’, with the increased sourness masking the sweet, wort-like characteristics of the NAB. Moreover, this NAB was ranked as the most highly acceptable in the sensory evaluation. In conclusion, the limited co-fermentation of non-Saccharomyces yeasts with LAB is a promising strategy for the production of NAB.},
 bibtype = {article},
 author = {Nyhan, Laura and Sahin, Aylin W. and Arendt, Elke K.},
 doi = {10.1007/S00217-022-04142-4/FIGURES/3},
 journal = {European Food Research and Technology},
 number = {1}
}

The non-alcoholic beer (NAB) sector has experienced steady growth in recent years, with breweries continuously seeking new ways to fulfil consumer demands. NAB can be produced by limited fermentation of non-Saccharomyces yeasts; however, beer produced in this manner is often critiqued for its sweet taste and wort-like off-flavours due to high levels of residual sugars and lack of flavour metabolites. The use of Lactobacillus in limited co-fermentation with non-Saccharomyces yeasts is a novel approach to produce NABs with varying flavour and aroma characteristics. In this study, lab-scale fermentations of Lachancea fermentati KBI 12.1 and Cyberlindnera subsufficiens C6.1 with Lactiplantibacillus plantarum FST 1.7 were performed and compared to a brewer’s yeast, Saccharomyces cerevisiae WLP001. Fermentations were monitored for pH, TTA, extract reduction, alcohol production, and microbial cell count. The final beers were analysed for sugar and organic acid concentration, free amino nitrogen content (FAN), glycerol, and levels of volatile metabolites. The inability of the non-Saccharomyces yeasts to utilise maltotriose as an energy source resulted in extended fermentation times compared to S. cerevisiae WLP001. Co-fermentation of yeasts with lactic acid bacteria (LAB) resulted in a decreased pH, higher TTA and increased levels of lactic acid in the final beers. The overall acceptability of the NABs produced by co-fermentation was higher than or similar to that of the beers fermented with the yeasts alone, indicating that LAB fermentation did not negatively impact the sensory attributes of the beer. C. subsufficiens C6.1 and L. plantarum FST 1.7 NAB was characterised as fruity tasting with the significantly higher ester concentrations masking the wort-like flavours resulting from limited fermentation. NAB produced with L. fermentati KBI12.1 and L. plantarum FST1.7 had decreased levels of the undesirable volatile compound diacetyl and was described as ‘fruity’ and ‘acidic’, with the increased sourness masking the sweet, wort-like characteristics of the NAB. Moreover, this NAB was ranked as the most highly acceptable in the sensory evaluation. In conclusion, the limited co-fermentation of non-Saccharomyces yeasts with LAB is a promising strategy for the production of NAB.

@article{
 title = {In vitro and in silico assessment of probiotic and functional properties of Bacillus subtilis DE111®},
 type = {article},
 year = {2023},
 keywords = {SCFA},
 volume = {13},
 websites = {https://pubmed.ncbi.nlm.nih.gov/36713219/},
 month = {1},
 publisher = {Front Microbiol},
 day = {13},
 id = {0f2a64e7-d3be-3e49-a47e-bb6eb5c929fc},
 created = {2025-07-07T13:25:42.067Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:42.067Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Bacillus subtilis DE111® is a safe, well-tolerated commercially available spore-forming probiotic that has been clinically shown to support a healthy gut microbiome, and to promote digestive and immune health in both adults and children. Recently it was shown that this spore-forming probiotic was capable of germinating in the gastrointestinal tract as early as 3 h after ingestion. However, a better understanding of the mechanisms involved in the efficacy of DE111® is required. Therefore, the present investigation was undertaken to elucidate the functional properties of DE111® through employing a combination of in vitro functional assays and genome analysis. DE111® genome mining revealed the presence of several genes encoding acid and stress tolerance mechanisms in addition to adhesion proteins required to survive and colonize harsh gastrointestinal environment including multi subunit ATPases, arginine deiminase (ADI) pathway genes (argBDR), stress (GroES/GroEL and DnaK/DnaJ) and extracellular polymeric substances (EPS) biosynthesis genes (pgsBCA). DE111® harbors several genes encoding enzymes involved in the metabolism of dietary molecules (protease, lipases, and carbohyrolases), antioxidant activity and genes associated with the synthesis of several B-vitamins (thiamine, riboflavin, pyridoxin, biotin, and folate), vitamin K2 (menaquinone) and seven amino acids including five essential amino acids (threonine, tryptophan, methionine, leucine, and lysine). Furthermore, a combined in silico analysis of bacteriocin producing genes with in vitro analysis highlighted a broad antagonistic activity of DE111® toward numerous urinary tract, intestinal, and skin pathogens. Enzymatic activities included proteases, peptidases, esterase’s, and carbohydrate metabolism coupled with metabolomic analysis of DE111® fermented ultra-high temperature milk, revealed a high release of amino acids and beneficial short chain fatty acids (SCFAs). Together, this study demonstrates the genetic and phenotypic ability of DE111® for surviving harsh gastric transit and conferring health benefits to the host, in particular its efficacy in the metabolism of dietary molecules, and its potential to generate beneficial SCFAs, casein-derived bioactive peptides, as well as its high antioxidant and antimicrobial potential. Thus, supporting the use of DE111® as a nutrient supplement and its pottential use in the preparation of functional foods.},
 bibtype = {article},
 author = {Mazhar, Shahneela and Khokhlova, Ekaterina and Colom, Joan and Simon, Annie and Deaton, John and Rea, Kieran},
 doi = {10.3389/FMICB.2022.1101144},
 journal = {Frontiers in microbiology}
}

Bacillus subtilis DE111® is a safe, well-tolerated commercially available spore-forming probiotic that has been clinically shown to support a healthy gut microbiome, and to promote digestive and immune health in both adults and children. Recently it was shown that this spore-forming probiotic was capable of germinating in the gastrointestinal tract as early as 3 h after ingestion. However, a better understanding of the mechanisms involved in the efficacy of DE111® is required. Therefore, the present investigation was undertaken to elucidate the functional properties of DE111® through employing a combination of in vitro functional assays and genome analysis. DE111® genome mining revealed the presence of several genes encoding acid and stress tolerance mechanisms in addition to adhesion proteins required to survive and colonize harsh gastrointestinal environment including multi subunit ATPases, arginine deiminase (ADI) pathway genes (argBDR), stress (GroES/GroEL and DnaK/DnaJ) and extracellular polymeric substances (EPS) biosynthesis genes (pgsBCA). DE111® harbors several genes encoding enzymes involved in the metabolism of dietary molecules (protease, lipases, and carbohyrolases), antioxidant activity and genes associated with the synthesis of several B-vitamins (thiamine, riboflavin, pyridoxin, biotin, and folate), vitamin K2 (menaquinone) and seven amino acids including five essential amino acids (threonine, tryptophan, methionine, leucine, and lysine). Furthermore, a combined in silico analysis of bacteriocin producing genes with in vitro analysis highlighted a broad antagonistic activity of DE111® toward numerous urinary tract, intestinal, and skin pathogens. Enzymatic activities included proteases, peptidases, esterase’s, and carbohydrate metabolism coupled with metabolomic analysis of DE111® fermented ultra-high temperature milk, revealed a high release of amino acids and beneficial short chain fatty acids (SCFAs). Together, this study demonstrates the genetic and phenotypic ability of DE111® for surviving harsh gastric transit and conferring health benefits to the host, in particular its efficacy in the metabolism of dietary molecules, and its potential to generate beneficial SCFAs, casein-derived bioactive peptides, as well as its high antioxidant and antimicrobial potential. Thus, supporting the use of DE111® as a nutrient supplement and its pottential use in the preparation of functional foods.

@article{
 title = {Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients},
 type = {article},
 year = {2023},
 keywords = {MCF,semi-polar},
 volume = {24},
 websites = {/pmc/articles/PMC9916682/,/pmc/articles/PMC9916682/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916682/},
 month = {2},
 publisher = {MDPI},
 day = {1},
 id = {c8ad95ce-f868-3a51-96d6-fa04859ba980},
 created = {2025-07-07T13:25:42.399Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:25.649Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {In trauma patients, shock-induced endotheliopathy (SHINE) is associated with a poor prognosis. We have previously identified four metabolic phenotypes in a small cohort of trauma patients (N = 20) and displayed the intracellular metabolic profile of the endothelial cell by integrating quantified plasma metabolomic profiles into a genome-scale metabolic model (iEC-GEM). A retrospective observational study of 99 trauma patients admitted to a Level 1 Trauma Center. Mass spectrometry was conducted on admission samples of plasma metabolites. Quantified metabolites were analyzed by computational network analysis of the iEC-GEM. Four plasma metabolic phenotypes (A–D) were identified, of which phenotype D was associated with an increased injury severity score (p < 0.001); 90% (91.6%) of the patients who died within 72 h possessed this phenotype. The inferred EC metabolic patterns were found to be different between phenotype A and D. Phenotype D was unable to maintain adequate redox homeostasis. We confirm that trauma patients presented four metabolic phenotypes at admission. Phenotype D was associated with increased mortality. Different EC metabolic patterns were identified between phenotypes A and D, and the inability to maintain adequate redox balance may be linked to the high mortality.},
 bibtype = {article},
 author = {Henriksen, Hanne H. and Marín de Mas, Igor and Nielsen, Lars K. and Krocker, Joseph and Stensballe, Jakob and Karvelsson, Sigurður T. and Secher, Niels H. and Rolfsson, Óttar and Wade, Charles E. and Johansson, Pär I.},
 doi = {10.3390/IJMS24032257/S1},
 journal = {International Journal of Molecular Sciences},
 number = {3}
}

In trauma patients, shock-induced endotheliopathy (SHINE) is associated with a poor prognosis. We have previously identified four metabolic phenotypes in a small cohort of trauma patients (N = 20) and displayed the intracellular metabolic profile of the endothelial cell by integrating quantified plasma metabolomic profiles into a genome-scale metabolic model (iEC-GEM). A retrospective observational study of 99 trauma patients admitted to a Level 1 Trauma Center. Mass spectrometry was conducted on admission samples of plasma metabolites. Quantified metabolites were analyzed by computational network analysis of the iEC-GEM. Four plasma metabolic phenotypes (A–D) were identified, of which phenotype D was associated with an increased injury severity score (p < 0.001); 90% (91.6%) of the patients who died within 72 h possessed this phenotype. The inferred EC metabolic patterns were found to be different between phenotype A and D. Phenotype D was unable to maintain adequate redox homeostasis. We confirm that trauma patients presented four metabolic phenotypes at admission. Phenotype D was associated with increased mortality. Different EC metabolic patterns were identified between phenotypes A and D, and the inability to maintain adequate redox balance may be linked to the high mortality.

@article{
 title = {Hepatocyte mARC1 promotes fatty liver disease},
 type = {article},
 year = {2023},
 keywords = {semi-polar},
 volume = {5},
 websites = {https://pubmed.ncbi.nlm.nih.gov/37122688/},
 month = {5},
 publisher = {JHEP Rep},
 day = {1},
 id = {9b9e0be4-e924-3394-b8cb-b525b3599767},
 created = {2025-07-07T13:25:42.775Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:26.014Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background & Aims: Non-alcoholic fatty liver disease (NAFLD) has a prevalence of ∼25% worldwide, with significant public health consequences yet few effective treatments. Human genetics can help elucidate novel biology and identify targets for new therapeutics. Genetic variants in mitochondrial amidoxime-reducing component 1 (MTARC1) have been associated with NAFLD and liver-related mortality; however, its pathophysiological role and the cell type(s) mediating these effects remain unclear. We aimed to investigate how MTARC1 exerts its effects on NAFLD by integrating human genetics with in vitro and in vivo studies of mARC1 knockdown. Methods: Analyses including multi-trait colocalisation and Mendelian randomisation were used to assess the genetic associations of MTARC1. In addition, we established an in vitro long-term primary human hepatocyte model with metabolic readouts and used the Gubra Amylin NASH (GAN)-diet non-alcoholic steatohepatitis mouse model treated with hepatocyte-specific N-acetylgalactosamine (GalNAc)–siRNA to understand the in vivo impacts of MTARC1. Results: We showed that genetic variants within the MTARC1 locus are associated with liver enzymes, liver fat, plasma lipids, and body composition, and these associations are attributable to the same causal variant (p.A165T, rs2642438 G>A), suggesting a shared mechanism. We demonstrated that increased MTARC1 mRNA had an adverse effect on these traits using Mendelian randomisation, implying therapeutic inhibition of mARC1 could be beneficial. In vitro mARC1 knockdown decreased lipid accumulation and increased triglyceride secretion, and in vivo GalNAc–siRNA-mediated knockdown of mARC1 lowered hepatic but increased plasma triglycerides. We found alterations in pathways regulating lipid metabolism and decreased secretion of 3-hydroxybutyrate upon mARC1 knockdown in vitro and in vivo. Conclusions: Collectively, our findings from human genetics, and in vitro and in vivo hepatocyte-specific mARC1 knockdown support the potential efficacy of hepatocyte-specific targeting of mARC1 for treatment of NAFLD. Impact and implications: We report that genetically predicted increases in MTARC1 mRNA associate with poor liver health. Furthermore, knockdown of mARC1 reduces hepatic steatosis in primary human hepatocytes and a murine NASH model. Together, these findings further underscore the therapeutic potential of targeting hepatocyte MTARC1 for NAFLD.},
 bibtype = {article},
 author = {Lewis, Lara C. and Chen, Lingyan and Hameed, L. Shahul and Kitchen, Robert R. and Maroteau, Cyrielle and Nagarajan, Shilpa R. and Norlin, Jenny and Daly, Charlotte E. and Szczerbinska, Iwona and Hjuler, Sara Toftegaard and Patel, Rahul and Livingstone, Eilidh J. and Durrant, Tom N. and Wondimu, Elisabeth and BasuRay, Soumik and Chandran, Anandhakumar and Lee, Wan Hung and Hu, Sile and Gilboa, Barak and Grandi, Megan E. and Toledo, Enrique M. and Erikat, Abdullah H.A. and Hodson, Leanne and Haynes, William G. and Pursell, Natalie W. and Coppieters, Ken and Fleckner, Jan and Howson, Joanna M.M. and Andersen, Birgitte and Ruby, Maxwell A.},
 doi = {10.1016/J.JHEPR.2023.100693},
 journal = {JHEP reports : innovation in hepatology},
 number = {5}
}

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) has a prevalence of ∼25% worldwide, with significant public health consequences yet few effective treatments. Human genetics can help elucidate novel biology and identify targets for new therapeutics. Genetic variants in mitochondrial amidoxime-reducing component 1 (MTARC1) have been associated with NAFLD and liver-related mortality; however, its pathophysiological role and the cell type(s) mediating these effects remain unclear. We aimed to investigate how MTARC1 exerts its effects on NAFLD by integrating human genetics with in vitro and in vivo studies of mARC1 knockdown. Methods: Analyses including multi-trait colocalisation and Mendelian randomisation were used to assess the genetic associations of MTARC1. In addition, we established an in vitro long-term primary human hepatocyte model with metabolic readouts and used the Gubra Amylin NASH (GAN)-diet non-alcoholic steatohepatitis mouse model treated with hepatocyte-specific N-acetylgalactosamine (GalNAc)–siRNA to understand the in vivo impacts of MTARC1. Results: We showed that genetic variants within the MTARC1 locus are associated with liver enzymes, liver fat, plasma lipids, and body composition, and these associations are attributable to the same causal variant (p.A165T, rs2642438 G>A), suggesting a shared mechanism. We demonstrated that increased MTARC1 mRNA had an adverse effect on these traits using Mendelian randomisation, implying therapeutic inhibition of mARC1 could be beneficial. In vitro mARC1 knockdown decreased lipid accumulation and increased triglyceride secretion, and in vivo GalNAc–siRNA-mediated knockdown of mARC1 lowered hepatic but increased plasma triglycerides. We found alterations in pathways regulating lipid metabolism and decreased secretion of 3-hydroxybutyrate upon mARC1 knockdown in vitro and in vivo. Conclusions: Collectively, our findings from human genetics, and in vitro and in vivo hepatocyte-specific mARC1 knockdown support the potential efficacy of hepatocyte-specific targeting of mARC1 for treatment of NAFLD. Impact and implications: We report that genetically predicted increases in MTARC1 mRNA associate with poor liver health. Furthermore, knockdown of mARC1 reduces hepatic steatosis in primary human hepatocytes and a murine NASH model. Together, these findings further underscore the therapeutic potential of targeting hepatocyte MTARC1 for NAFLD.

@article{
 title = {Acute physiological effects following Bacillus subtilis DE111 oral ingestion - a randomised, double blinded, placebo-controlled study},
 type = {article},
 year = {2023},
 keywords = {semi-polar},
 pages = {31-43},
 volume = {14},
 websites = {https://pubmed.ncbi.nlm.nih.gov/36790091/},
 publisher = {Benef Microbes},
 id = {4a7b2590-3ec8-39f7-a742-60256c00797b},
 created = {2025-07-07T13:25:43.104Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:26.363Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Previous studies using ileostomy samples from study participants demonstrated that the spore-forming probiotic Bacillus subtilis DE111® can germinate in the small intestine as early as 4 hours after ingestion. Metabolomics, proteomics and sequencing technologies, enabled further analysis of these samples for the presence of hypoglycaemic, hypolipidemic, antioxidant, anti-inflammatory and antihypertensive molecules. In the DE111 treatment group, the polyphenols trigonelline and 2,5-dihydroxybenzoic acid, orotic acid, the non-essential amino acid cystine and the lipokine 12,13-diHome were increased. DE111 also reduced acetylcholine levels in the ileostomy samples, and increased the expression of leucocyte recruiting proteins, antimicrobial peptides and intestinal alkaline phosphatases of the brush border in the small intestine. The combination of B. subtilis DE111 and the diet administered during the study increased the expression of the proteins phosphodiesterase ENPP7, ceramidase ASAH2 and the adipokine Zn-alpha-2-glycoprotein that are involved in fatty acid and lipid metabolism. Acute B. subtilis DE111 ingestion had limited detectable effect on the microbiome, with the main change being its increased presence. These findings support previous data suggesting a beneficial role of DE111 in digestion, metabolism, and immune health that appears to begin within hours of consumption.},
 bibtype = {article},
 author = {Colom, J. and Freitas, D. and Simon, A. and Khokhlova, E. and Mazhar, S. and Buckley, M. and Phipps, C. and Deaton, J. and Brodkorb, A. and Rea, K.},
 doi = {10.3920/BM2022.0081},
 journal = {Beneficial microbes},
 number = {1}
}

Previous studies using ileostomy samples from study participants demonstrated that the spore-forming probiotic Bacillus subtilis DE111® can germinate in the small intestine as early as 4 hours after ingestion. Metabolomics, proteomics and sequencing technologies, enabled further analysis of these samples for the presence of hypoglycaemic, hypolipidemic, antioxidant, anti-inflammatory and antihypertensive molecules. In the DE111 treatment group, the polyphenols trigonelline and 2,5-dihydroxybenzoic acid, orotic acid, the non-essential amino acid cystine and the lipokine 12,13-diHome were increased. DE111 also reduced acetylcholine levels in the ileostomy samples, and increased the expression of leucocyte recruiting proteins, antimicrobial peptides and intestinal alkaline phosphatases of the brush border in the small intestine. The combination of B. subtilis DE111 and the diet administered during the study increased the expression of the proteins phosphodiesterase ENPP7, ceramidase ASAH2 and the adipokine Zn-alpha-2-glycoprotein that are involved in fatty acid and lipid metabolism. Acute B. subtilis DE111 ingestion had limited detectable effect on the microbiome, with the main change being its increased presence. These findings support previous data suggesting a beneficial role of DE111 in digestion, metabolism, and immune health that appears to begin within hours of consumption.

@article{
 title = {Metabolomic profiles in relapsing-remitting and progressive multiple sclerosis compared to healthy controls: a five-year follow-up study},
 type = {article},
 year = {2023},
 keywords = {semi-polar},
 volume = {19},
 websites = {https://pubmed.ncbi.nlm.nih.gov/37079261/},
 month = {5},
 publisher = {Metabolomics},
 day = {1},
 id = {c3c89244-00f0-3eb2-9c68-53a7bdb7bc47},
 created = {2025-07-07T13:25:43.435Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:26.783Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction and objectives: Multiple sclerosis (MS) is a disease of the central nervous system associated with immune dysfunction, demyelination, and neurodegeneration. The disease has heterogeneous clinical phenotypes such as relapsing–remitting MS (RRMS) and progressive multiple sclerosis (PMS), each with unique pathogenesis. Metabolomics research has shown promise in understanding the etiologies of MS disease. However, there is a paucity of clinical studies with follow-up metabolomics analyses. This 5-year follow-up (5YFU) cohort study aimed to investigate the metabolomics alterations over time between different courses of MS patients and healthy controls and provide insights into metabolic and physiological mechanisms of MS disease progression. Methods: A cohort containing 108 MS patients (37 PMS and 71 RRMS) and 42 controls were followed up for a median of 5 years. Liquid chromatography–mass spectrometry (LC–MS) was applied for untargeted metabolomics profiling of serum samples of the cohort at both baseline and 5YFU. Univariate analyses with mixed-effect ANCOVA models, clustering, and pathway enrichment analyses were performed to identify patterns of metabolites and pathway changes across the time effects and patient groups. Results and conclusions: Out of 592 identified metabolites, the PMS group exhibited the most changes, with 219 (37%) metabolites changed over time and 132 (22%) changed within the RRMS group (Bonferroni adjusted P < 0.05). Compared to the baseline, there were more significant metabolite differences detected between PMS and RRMS classes at 5YFU. Pathway enrichment analysis detected seven pathways perturbed significantly during 5YFU in MS groups compared to controls. PMS showed more pathway changes compared to the RRMS group.},
 bibtype = {article},
 author = {Shi, Tiange and Browne, Richard W. and Tamaño-Blanco, Miriam and Jakimovski, Dejan and Weinstock-Guttman, Bianca and Zivadinov, Robert and Ramanathan, Murali and Blair, Rachael H.},
 doi = {10.1007/S11306-023-02010-0},
 journal = {Metabolomics : Official journal of the Metabolomic Society},
 number = {5}
}

Introduction and objectives: Multiple sclerosis (MS) is a disease of the central nervous system associated with immune dysfunction, demyelination, and neurodegeneration. The disease has heterogeneous clinical phenotypes such as relapsing–remitting MS (RRMS) and progressive multiple sclerosis (PMS), each with unique pathogenesis. Metabolomics research has shown promise in understanding the etiologies of MS disease. However, there is a paucity of clinical studies with follow-up metabolomics analyses. This 5-year follow-up (5YFU) cohort study aimed to investigate the metabolomics alterations over time between different courses of MS patients and healthy controls and provide insights into metabolic and physiological mechanisms of MS disease progression. Methods: A cohort containing 108 MS patients (37 PMS and 71 RRMS) and 42 controls were followed up for a median of 5 years. Liquid chromatography–mass spectrometry (LC–MS) was applied for untargeted metabolomics profiling of serum samples of the cohort at both baseline and 5YFU. Univariate analyses with mixed-effect ANCOVA models, clustering, and pathway enrichment analyses were performed to identify patterns of metabolites and pathway changes across the time effects and patient groups. Results and conclusions: Out of 592 identified metabolites, the PMS group exhibited the most changes, with 219 (37%) metabolites changed over time and 132 (22%) changed within the RRMS group (Bonferroni adjusted P < 0.05). Compared to the baseline, there were more significant metabolite differences detected between PMS and RRMS classes at 5YFU. Pathway enrichment analysis detected seven pathways perturbed significantly during 5YFU in MS groups compared to controls. PMS showed more pathway changes compared to the RRMS group.

@article{
 title = {Skin mucus metabolomics provides insights into the interplay between diet and wound in gilthead seabream (Sparus aurata)},
 type = {article},
 year = {2023},
 keywords = {semi-polar},
 volume = {134},
 websites = {https://pubmed.ncbi.nlm.nih.gov/36746227/},
 month = {3},
 publisher = {Fish Shellfish Immunol},
 day = {1},
 id = {291d03ed-fc68-304e-b585-d821afcec792},
 created = {2025-07-07T13:25:43.796Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:27.212Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The molecular processes underlying skin wound healing in several fish species have been elucidated in the last years, however, metabolomic insights are scarce. Here we report the skin mucus metabolome of wounded and non-wounded gilthead seabream (Sparus aurata) fed with silk fibroin microparticles, a functional additive considered to accelerate the wound healing process. The three experimental diets (commercial diet enriched with 0 mg (control), 50 mg or 100 mg of silk fibroin microparticles Kg−1) were administered for 30 days and thereafter, a skin wound was inflicted. Skin mucus was collected on day 30 of feeding and 7 days post-wounding and subjected to metabolomic analysis by Ultra Performance Liquid Chromatography coupled with a high-resolution quadrupole-orbitrap mass spectrometry. The most enriched metabolite class was amino acids and derivatives, followed by nucleotides, nucleosides and analogues and carbohydrates and their derivatives. Metabolomic profiles revealed that the diet had a more profound effect than wounding in skin mucus. Metabolic pathway analysis of significantly affected metabolites revealed perturbations in the aminoacyl t-RNA biosynthesis in the skin. In particular, skin wound resulted in a decreased methionine level in mucus. Further, silk fibroin supplementation increased methionine level in skin mucus, which correlated with several wound morphometric parameters that characterized the epithelial healing capacity in seabream. The results provided new insight into the physiological consequences of skin wounds and how these processes could be influenced by dietary manipulation.},
 bibtype = {article},
 author = {Albaladejo-Riad, Nora and Espinosa-Ruiz, Cristóbal and Esteban, María Ángeles and Lazado, Carlo C.},
 doi = {10.1016/J.FSI.2023.108590},
 journal = {Fish & shellfish immunology}
}

The molecular processes underlying skin wound healing in several fish species have been elucidated in the last years, however, metabolomic insights are scarce. Here we report the skin mucus metabolome of wounded and non-wounded gilthead seabream (Sparus aurata) fed with silk fibroin microparticles, a functional additive considered to accelerate the wound healing process. The three experimental diets (commercial diet enriched with 0 mg (control), 50 mg or 100 mg of silk fibroin microparticles Kg−1) were administered for 30 days and thereafter, a skin wound was inflicted. Skin mucus was collected on day 30 of feeding and 7 days post-wounding and subjected to metabolomic analysis by Ultra Performance Liquid Chromatography coupled with a high-resolution quadrupole-orbitrap mass spectrometry. The most enriched metabolite class was amino acids and derivatives, followed by nucleotides, nucleosides and analogues and carbohydrates and their derivatives. Metabolomic profiles revealed that the diet had a more profound effect than wounding in skin mucus. Metabolic pathway analysis of significantly affected metabolites revealed perturbations in the aminoacyl t-RNA biosynthesis in the skin. In particular, skin wound resulted in a decreased methionine level in mucus. Further, silk fibroin supplementation increased methionine level in skin mucus, which correlated with several wound morphometric parameters that characterized the epithelial healing capacity in seabream. The results provided new insight into the physiological consequences of skin wounds and how these processes could be influenced by dietary manipulation.

@article{
 title = {Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis},
 type = {article},
 year = {2023},
 keywords = {semi-polar},
 pages = {4916-4934},
 volume = {146},
 websites = {https://dx.doi.org/10.1093/brain/awad303},
 month = {12},
 publisher = {Oxford Academic},
 day = {1},
 id = {5b4d0d1a-1d59-3a85-812a-cb364b19bbe1},
 created = {2025-07-07T13:25:44.134Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:27.585Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Alzheimer's disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer's disease by showing specific alterations in the gut microbiome composition of Alzheimer's patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer's symptoms. To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera. Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.},
 bibtype = {article},
 author = {Grabrucker, Stefanie and Marizzoni, Moira and Silajžić, Edina and Lopizzo, Nicola and Mombelli, Elisa and Nicolas, Sarah and Dohm-Hansen, Sebastian and Scassellati, Catia and Moretti, Davide Vito and Rosa, Melissa and Hoffmann, Karina and Cryan, John F. and O'Leary, Olivia F. and English, Jane A. and Lavelle, Aonghus and O'Neill, Cora and Thuret, Sandrine and Cattaneo, Annamaria and Nolan, Yvonne M.},
 doi = {10.1093/BRAIN/AWAD303},
 journal = {Brain},
 number = {12}
}

Alzheimer's disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer's disease by showing specific alterations in the gut microbiome composition of Alzheimer's patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer's symptoms. To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera. Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.

@article{
 title = {Gut microbes predominantly act as living beneficial partners rather than raw nutrients},
 type = {article},
 year = {2023},
 keywords = {Microbiology,Physiology},
 pages = {1-12},
 volume = {13},
 websites = {https://www.nature.com/articles/s41598-023-38669-7},
 month = {7},
 publisher = {Nature Publishing Group},
 day = {24},
 id = {ad39e1bf-7658-36c0-a9cc-eb662151265c},
 created = {2025-07-07T13:25:44.448Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:27.963Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Animals and their gut microbes mutually benefit their health. Nutrition plays a central role in this, directly influencing both host and microbial fitness and the nature of their interactions. This makes nutritional symbioses a complex and dynamic tri-system of diet-microbiota-host. Despite recent discoveries on this field, full control over the interplay among these partners is challenging and hinders the resolution of fundamental questions, such as how to parse the gut microbes’ effect as raw nutrition or as symbiotic partners? To tackle this, we made use of the well-characterized Drosophila melanogaster/Lactiplantibacillus plantarum experimental model of nutritional symbiosis to generate a quantitative framework of gut microbes’ effect on the host. By coupling experimental assays and Random Forest analysis, we show that the beneficial effect of L. plantarum strains primarily results from the active relationship as symbionts rather than raw nutrients, regardless of the bacterial strain. Metabolomic analysis of both active and inactive bacterial cells further demonstrated the crucial role of the production of beneficial bacterial metabolites, such as N-acetylated-amino-acids, as result of active bacterial growth and function. Altogether, our results provide a ranking and quantification of the main bacterial features contributing to sustain animal growth. We demonstrate that bacterial activity is the predominant and necessary variable involved in bacteria-mediated benefit, followed by strain-specific properties and the nutritional potential of the bacterial cells. This contributes to elucidate the role of beneficial bacteria and probiotics, creating a broad quantitative framework for host-gut microbiome that can be expanded to other model systems.},
 bibtype = {article},
 author = {da Silva Soares, Nuno Filipe and Quagliariello, Andrea and Yigitturk, Seren and Martino, Maria Elena},
 doi = {10.1038/s41598-023-38669-7},
 journal = {Scientific Reports 2023 13:1},
 number = {1}
}

Animals and their gut microbes mutually benefit their health. Nutrition plays a central role in this, directly influencing both host and microbial fitness and the nature of their interactions. This makes nutritional symbioses a complex and dynamic tri-system of diet-microbiota-host. Despite recent discoveries on this field, full control over the interplay among these partners is challenging and hinders the resolution of fundamental questions, such as how to parse the gut microbes’ effect as raw nutrition or as symbiotic partners? To tackle this, we made use of the well-characterized Drosophila melanogaster/Lactiplantibacillus plantarum experimental model of nutritional symbiosis to generate a quantitative framework of gut microbes’ effect on the host. By coupling experimental assays and Random Forest analysis, we show that the beneficial effect of L. plantarum strains primarily results from the active relationship as symbionts rather than raw nutrients, regardless of the bacterial strain. Metabolomic analysis of both active and inactive bacterial cells further demonstrated the crucial role of the production of beneficial bacterial metabolites, such as N-acetylated-amino-acids, as result of active bacterial growth and function. Altogether, our results provide a ranking and quantification of the main bacterial features contributing to sustain animal growth. We demonstrate that bacterial activity is the predominant and necessary variable involved in bacteria-mediated benefit, followed by strain-specific properties and the nutritional potential of the bacterial cells. This contributes to elucidate the role of beneficial bacteria and probiotics, creating a broad quantitative framework for host-gut microbiome that can be expanded to other model systems.

@article{
 title = {NAD+ regulates nucleotide metabolism and genomic DNA replication},
 type = {article},
 year = {2023},
 keywords = {polar},
 pages = {1774-1786},
 volume = {25},
 websites = {https://www.nature.com/articles/s41556-023-01280-z},
 month = {11},
 publisher = {Nature Publishing Group},
 day = {13},
 id = {78495bc8-2f97-3e07-b54a-c772548f9d9b},
 created = {2025-07-07T13:25:44.780Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:28.321Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The intricate orchestration of enzymatic activities involving nicotinamide adenine dinucleotide (NAD+) is essential for maintaining metabolic homeostasis and preserving genomic integrity. As a co-enzyme, NAD+ plays a key role in regulating metabolic pathways, such as glycolysis and Kreb’s cycle. ADP-ribosyltransferases (PARPs) and sirtuins rely on NAD+ to mediate post-translational modifications of target proteins. The activation of PARP1 in response to DNA breaks leads to rapid depletion of cellular NAD+ compromising cell viability. Therefore, the levels of NAD+ must be tightly regulated. Here we show that exogenous NAD+, but not its precursors, has a direct effect on mitochondrial activity. Short-term incubation with NAD+ boosts Kreb’s cycle and the electron transport chain and enhances pyrimidine biosynthesis. Extended incubation with NAD+ results in depletion of pyrimidines, accumulation of purines, activation of the replication stress response and cell cycle arrest. Moreover, a combination of NAD+ and 5-fluorouridine selectively kills cancer cells that rely on de novo pyrimidine synthesis. We propose an integrated model of how NAD+ regulates nucleotide metabolism, with relevance to healthspan, ageing and cancer therapy. Munk et al. show that exogenous NAD+, but not its precursors, induces metabolic changes in mitochondria affecting nucleotide metabolism with impacts on genomic DNA synthesis and genome integrity.},
 bibtype = {article},
 author = {Munk, Sebastian Howen Nesgaard and Merchut-Maya, Joanna Maria and Adelantado Rubio, Alba and Hall, Arnaldur and Pappas, George and Milletti, Giacomo and Lee, Myung Hee and Johnsen, Lea Giørtz and Guldberg, Per and Bartek, Jiri and Maya-Mendoza, Apolinar},
 doi = {10.1038/s41556-023-01280-z},
 journal = {Nature Cell Biology 2023 25:12},
 number = {12}
}

The intricate orchestration of enzymatic activities involving nicotinamide adenine dinucleotide (NAD+) is essential for maintaining metabolic homeostasis and preserving genomic integrity. As a co-enzyme, NAD+ plays a key role in regulating metabolic pathways, such as glycolysis and Kreb’s cycle. ADP-ribosyltransferases (PARPs) and sirtuins rely on NAD+ to mediate post-translational modifications of target proteins. The activation of PARP1 in response to DNA breaks leads to rapid depletion of cellular NAD+ compromising cell viability. Therefore, the levels of NAD+ must be tightly regulated. Here we show that exogenous NAD+, but not its precursors, has a direct effect on mitochondrial activity. Short-term incubation with NAD+ boosts Kreb’s cycle and the electron transport chain and enhances pyrimidine biosynthesis. Extended incubation with NAD+ results in depletion of pyrimidines, accumulation of purines, activation of the replication stress response and cell cycle arrest. Moreover, a combination of NAD+ and 5-fluorouridine selectively kills cancer cells that rely on de novo pyrimidine synthesis. We propose an integrated model of how NAD+ regulates nucleotide metabolism, with relevance to healthspan, ageing and cancer therapy. Munk et al. show that exogenous NAD+, but not its precursors, induces metabolic changes in mitochondria affecting nucleotide metabolism with impacts on genomic DNA synthesis and genome integrity.

@article{
 title = {NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease},
 type = {article},
 year = {2023},
 keywords = {Drug safety,Parkinson's disease,Randomized controlled trials},
 pages = {1-13},
 volume = {14},
 websites = {https://www.nature.com/articles/s41467-023-43514-6},
 month = {11},
 publisher = {Nature Publishing Group},
 day = {28},
 id = {efeded12-b3af-363c-976e-a4f8694983bf},
 created = {2025-07-07T13:25:45.310Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:28.672Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Nicotinamide adenine dinucleotide (NAD) replenishment therapy using nicotinamide riboside (NR) shows promise for Parkinson’s disease (PD) and other neurodegenerative disorders. However, the optimal dose of NR remains unknown, and doses exceeding 2000 mg daily have not been tested in humans. To evaluate the safety of high-dose NR therapy, we conducted a single-center, randomized, placebo-controlled, double-blind, phase I trial on 20 individuals with PD, randomized 1:1 on NR 1500 mg twice daily (n = 10) or placebo (n = 10) for four weeks. The trial was conducted at the Department of Neurology, Haukeland University Hospital, Bergen, Norway. The primary outcome was safety, defined as the frequency of moderate and severe adverse events. Secondary outcomes were tolerability defined as frequency of mild adverse events, change in the whole blood and urine NAD metabolome, and change in the clinical severity of PD, measured by MDS-UPDRS. All 20 participants completed the trial. The trial met all prespecified outcomes. NR therapy was well tolerated with no moderate or severe adverse events, and no significant difference in mild adverse events. NR therapy was associated with clinical improvement of total MDS-UPDRS scores. However, this change was also associated with a shorter interval since the last levodopa dose. NR greatly augmented the blood NAD metabolome with up to 5-fold increase in blood NAD+ levels. While NR-recipients exhibited a slight initial rise in serum homocysteine levels, the integrity of the methyl donor pool remained intact. Our results support extending the dose range of NR in phase II clinical trials to 3000 mg per day, with appropriate safety monitoring. Clinicaltrials.gov identifier: NCT05344404. Oral nicotinamide riboside (NR) at a dose of 3000 mg daily for 30 days is safe and associated with a pronounced systemic augmentation of the NAD metabolome, but no methyl donor depletion.},
 bibtype = {article},
 author = {Berven, Haakon and Kverneng, Simon and Sheard, Erika and Søgnen, Mona and Af Geijerstam, Solveig Amdahl and Haugarvoll, Kristoffer and Skeie, Geir Olve and Dölle, Christian and Tzoulis, Charalampos},
 doi = {10.1038/s41467-023-43514-6},
 journal = {Nature Communications 2023 14:1},
 number = {1}
}

Nicotinamide adenine dinucleotide (NAD) replenishment therapy using nicotinamide riboside (NR) shows promise for Parkinson’s disease (PD) and other neurodegenerative disorders. However, the optimal dose of NR remains unknown, and doses exceeding 2000 mg daily have not been tested in humans. To evaluate the safety of high-dose NR therapy, we conducted a single-center, randomized, placebo-controlled, double-blind, phase I trial on 20 individuals with PD, randomized 1:1 on NR 1500 mg twice daily (n = 10) or placebo (n = 10) for four weeks. The trial was conducted at the Department of Neurology, Haukeland University Hospital, Bergen, Norway. The primary outcome was safety, defined as the frequency of moderate and severe adverse events. Secondary outcomes were tolerability defined as frequency of mild adverse events, change in the whole blood and urine NAD metabolome, and change in the clinical severity of PD, measured by MDS-UPDRS. All 20 participants completed the trial. The trial met all prespecified outcomes. NR therapy was well tolerated with no moderate or severe adverse events, and no significant difference in mild adverse events. NR therapy was associated with clinical improvement of total MDS-UPDRS scores. However, this change was also associated with a shorter interval since the last levodopa dose. NR greatly augmented the blood NAD metabolome with up to 5-fold increase in blood NAD+ levels. While NR-recipients exhibited a slight initial rise in serum homocysteine levels, the integrity of the methyl donor pool remained intact. Our results support extending the dose range of NR in phase II clinical trials to 3000 mg per day, with appropriate safety monitoring. Clinicaltrials.gov identifier: NCT05344404. Oral nicotinamide riboside (NR) at a dose of 3000 mg daily for 30 days is safe and associated with a pronounced systemic augmentation of the NAD metabolome, but no methyl donor depletion.

@article{
 title = {Low-no-calorie sweeteners exert marked compound-specific impact on the human gut microbiota ex vivo},
 type = {article},
 year = {2023},
 keywords = {Adult,Davide Risso,Diabetes Mellitus,Energy Intake,Gastrointestinal Microbiome*,Humans,Jonas Poppe,MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Pieter Van den Abbeele,Propionates,PubMed Abstract,Sorbitol,Stevia*,Sweetening Agents / pharmacology,Type 2*,doi:10.1080/09637486.2023.2240037,pmid:37537786},
 pages = {630-644},
 volume = {74},
 websites = {https://pubmed.ncbi.nlm.nih.gov/37537786/},
 publisher = {Int J Food Sci Nutr},
 id = {b3ae7917-7c69-36d3-bfcf-fe6c3cb766bb},
 created = {2025-07-07T13:25:45.693Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:45.693Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Low-no-calorie sweeteners (LNCS) are used as sugar substitutes as part of strategies to reduce the risk of chronic diseases related to high sugar intake (e.g. type 2 diabetes (T2D)). This study investigated how a range of sweeteners [tagatose (TA)/maltitol (MA)/sorbitol (SO)/stevia (ST)/sucralose (SU)/acesulfame K (ACK)] impact the gut microbiota of T2D subjects and healthy human adults using the ex vivo SIFR® technology (n = 12). The cohort covered clinically relevant interpersonal and T2D-related differences. ACK/SU remained intact while not impacting microbial composition and metabolite production. In contrast, TA/SO and ST/MA were respectively readily and gradually fermented. ST and particularly TA/SO/MA increased bacterial density and SCFA production product-specifically: SO increased acetate (∼Bifidobacterium adolescentis), whilst MA/ST increased propionate (∼Parabacteroides distasonis). TA exerted low specificity as it increased butyrate for healthy subjects, yet propionate for T2D subjects. Overall, LNCS exerted highly compound-specific effects stressing that results obtained for one LNCS cannot be generalised to other LNCS.},
 bibtype = {article},
 author = {Van den Abbeele, Pieter and Poppe, Jonas and Deyaert, Stef and Laurie, Ieva and Otto Gravert, Thorsten Klaus and Abrahamsson, Anna and Baudot, Aurélien and Karnik, Kavita and Risso, Davide},
 doi = {10.1080/09637486.2023.2240037},
 journal = {International journal of food sciences and nutrition},
 number = {5}
}

Low-no-calorie sweeteners (LNCS) are used as sugar substitutes as part of strategies to reduce the risk of chronic diseases related to high sugar intake (e.g. type 2 diabetes (T2D)). This study investigated how a range of sweeteners [tagatose (TA)/maltitol (MA)/sorbitol (SO)/stevia (ST)/sucralose (SU)/acesulfame K (ACK)] impact the gut microbiota of T2D subjects and healthy human adults using the ex vivo SIFR® technology (n = 12). The cohort covered clinically relevant interpersonal and T2D-related differences. ACK/SU remained intact while not impacting microbial composition and metabolite production. In contrast, TA/SO and ST/MA were respectively readily and gradually fermented. ST and particularly TA/SO/MA increased bacterial density and SCFA production product-specifically: SO increased acetate (∼Bifidobacterium adolescentis), whilst MA/ST increased propionate (∼Parabacteroides distasonis). TA exerted low specificity as it increased butyrate for healthy subjects, yet propionate for T2D subjects. Overall, LNCS exerted highly compound-specific effects stressing that results obtained for one LNCS cannot be generalised to other LNCS.

@article{
 title = {Oxygen Toxicity Causes Cyclic Damage by Destabilizing Specific Fe-S Cluster-Containing Protein Complexes},
 type = {article},
 year = {2023},
 keywords = {polar,semi-polar},
 pages = {942},
 volume = {83},
 websites = {/pmc/articles/PMC10148707/,/pmc/articles/PMC10148707/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148707/},
 month = {3},
 publisher = {NIH Public Access},
 day = {3},
 id = {e8b06420-f1bd-3b42-b821-f5eb653dccde},
 created = {2025-07-07T13:25:46.042Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:29.092Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Oxygen is toxic across all three domains of life. Yet, the underlying molecular mechanisms remain largely unknown. Here, we systematically investigate the major cellular pathways affected by excess molecular oxygen. We find that hyperoxia destabilizes a specific subset of Fe-S cluster (ISC)-containing proteins, resulting in impaired diphthamide synthesis, purine metabolism, nucleotide excision repair, and electron transport chain (ETC) function. Our findings translate to primary human lung cells and a mouse model of pulmonary oxygen toxicity. We demonstrate that the ETC is the most vulnerable to damage, resulting in decreased mitochondrial oxygen consumption. This leads to further tissue hyperoxia and cyclic damage of the additional ISC-containing pathways. In support of this model, primary ETC dysfunction in the Ndufs4 KO mouse model causes lung tissue hyperoxia and dramatically increases sensitivity to hyperoxia-mediated ISC damage. This work has important implications for hyperoxia pathologies, including bronchopulmonary dysplasia, ischemia-reperfusion injury, aging, and mitochondrial disorders.},
 bibtype = {article},
 author = {Baik, Alan H. and Haribowo, Augustinus G. and Chen, Xuewen and Queliconi, Bruno B. and Barrios, Alec M. and Garg, Ankur and Maishan, Mazharul and Campos, Alexandre R. and Matthay, Michael A. and Jain, Isha H.},
 doi = {10.1016/J.MOLCEL.2023.02.013},
 journal = {Molecular cell},
 number = {6}
}

Oxygen is toxic across all three domains of life. Yet, the underlying molecular mechanisms remain largely unknown. Here, we systematically investigate the major cellular pathways affected by excess molecular oxygen. We find that hyperoxia destabilizes a specific subset of Fe-S cluster (ISC)-containing proteins, resulting in impaired diphthamide synthesis, purine metabolism, nucleotide excision repair, and electron transport chain (ETC) function. Our findings translate to primary human lung cells and a mouse model of pulmonary oxygen toxicity. We demonstrate that the ETC is the most vulnerable to damage, resulting in decreased mitochondrial oxygen consumption. This leads to further tissue hyperoxia and cyclic damage of the additional ISC-containing pathways. In support of this model, primary ETC dysfunction in the Ndufs4 KO mouse model causes lung tissue hyperoxia and dramatically increases sensitivity to hyperoxia-mediated ISC damage. This work has important implications for hyperoxia pathologies, including bronchopulmonary dysplasia, ischemia-reperfusion injury, aging, and mitochondrial disorders.

@article{
 title = {Day-night fluctuations in choroid plexus transcriptomics and cerebrospinal fluid metabolomics},
 type = {article},
 year = {2023},
 keywords = {Beatriche Louise Edelbo,MEDLINE,NCBI,NIH,NLM,Nanna MacAulay,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,PMC10443925,PubMed Abstract,Søren Norge Andreassen,doi:10.1093/pnasnexus/pgad262,pmid:37614671},
 volume = {2},
 websites = {https://pubmed.ncbi.nlm.nih.gov/37614671/},
 month = {8},
 publisher = {PNAS Nexus},
 day = {1},
 id = {d84f8c8f-baf8-3b58-ab88-5eb0724dffe7},
 created = {2025-07-07T13:25:46.371Z},
 accessed = {2024-04-12},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:46.371Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The cerebrospinal fluid (CSF) provides mechanical protection for the brain and serves as a brain dispersion route for nutrients, hormones, and metabolic waste. The CSF secretion rate is elevated in the dark phase in both humans and rats, which could support the CSF flow along the paravascular spaces that may be implicated in waste clearance. The similar diurnal CSF dynamics pattern observed in the day-active human and the nocturnal rat suggests a circadian regulation of this physiological variable, rather than sleep itself. To obtain a catalog of potential molecular drivers that could provide the day-night-associated modulation of the CSF secretion rate, we determined the diurnal fluctuation in the rat choroid plexus transcriptomic profile with RNA-seq and in the CSF metabolomics with ultraperformance liquid chromatography combined with mass spectrometry. We detected significant fluctuation of 19 CSF metabolites and differential expression of 2,778 choroid plexus genes between the light and the dark phase, the latter of which encompassed circadian rhythm-related genes and several choroid plexus transport mechanisms. The fluctuating components were organized with joint pathway analysis, of which several pathways demonstrated diurnal regulation. Our results illustrate substantial transcriptional and metabolic light-dark phase-mediated changes taking place in the rat choroid plexus and its encircling CSF. The combined data provide directions toward future identification of the molecular pathways governing the fluctuation of this physiological process and could potentially be harnessed to modulate the CSF dynamics in pathology.},
 bibtype = {article},
 author = {Edelbo, Beatriche Louise and Andreassen, Søren Norge and Steffensen, Annette Buur and MacAulay, Nanna},
 doi = {10.1093/PNASNEXUS/PGAD262},
 journal = {PNAS nexus},
 number = {8}
}

The cerebrospinal fluid (CSF) provides mechanical protection for the brain and serves as a brain dispersion route for nutrients, hormones, and metabolic waste. The CSF secretion rate is elevated in the dark phase in both humans and rats, which could support the CSF flow along the paravascular spaces that may be implicated in waste clearance. The similar diurnal CSF dynamics pattern observed in the day-active human and the nocturnal rat suggests a circadian regulation of this physiological variable, rather than sleep itself. To obtain a catalog of potential molecular drivers that could provide the day-night-associated modulation of the CSF secretion rate, we determined the diurnal fluctuation in the rat choroid plexus transcriptomic profile with RNA-seq and in the CSF metabolomics with ultraperformance liquid chromatography combined with mass spectrometry. We detected significant fluctuation of 19 CSF metabolites and differential expression of 2,778 choroid plexus genes between the light and the dark phase, the latter of which encompassed circadian rhythm-related genes and several choroid plexus transport mechanisms. The fluctuating components were organized with joint pathway analysis, of which several pathways demonstrated diurnal regulation. Our results illustrate substantial transcriptional and metabolic light-dark phase-mediated changes taking place in the rat choroid plexus and its encircling CSF. The combined data provide directions toward future identification of the molecular pathways governing the fluctuation of this physiological process and could potentially be harnessed to modulate the CSF dynamics in pathology.

@article{
 title = {Age-associated deficits in social behaviour are microbiota-dependent},
 type = {article},
 year = {2023},
 keywords = {Aging,Metabolites,Microbiome,Social behaviour},
 pages = {119-124},
 volume = {110},
 month = {5},
 publisher = {Academic Press},
 day = {1},
 id = {e6c05544-746b-3a2e-8233-93c9a111aef7},
 created = {2025-07-07T13:25:46.768Z},
 accessed = {2025-01-07},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:29.531Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Aging is associated with remodelling of immune and central nervous system responses resulting in behavioural impairments including social deficits. Growing evidence suggests that the gut microbiome is also impacted by aging, and we propose that strategies to reshape the aged gut microbiome may ameliorate some age-related effects on host physiology. Thus, we assessed the impact of gut microbiota depletion, using an antibiotic cocktail, on aging and its impact on social behavior and the immune system. Indeed, microbiota depletion in aged mice eliminated the age-dependent deficits in social recognition. We further demonstrate that although age and gut microbiota depletion differently shape the peripheral immune response, aging induces an accumulation of T cells in the choroid plexus, that is partially blunted following microbiota depletion. Moreover, an untargeted metabolomic analysis revealed age-dependent alterations of cecal metabolites that are reshaped by gut microbiota depletion. Together, our results suggest that the aged gut microbiota can be specifically targeted to affect social deficits. These studies propel the need for future investigations of other non-antibiotic microbiota targeted interventions on age-related social deficits both in animal models and humans.},
 bibtype = {article},
 author = {Cruz-Pereira, Joana S. and Moloney, Gerard M. and Bastiaanssen, Thomaz F.S. and Boscaini, Serena and Fitzgerald, Patrick and Clarke, Gerard and Cryan, John F.},
 doi = {10.1016/J.BBI.2023.02.008},
 journal = {Brain, Behavior, and Immunity}
}

Aging is associated with remodelling of immune and central nervous system responses resulting in behavioural impairments including social deficits. Growing evidence suggests that the gut microbiome is also impacted by aging, and we propose that strategies to reshape the aged gut microbiome may ameliorate some age-related effects on host physiology. Thus, we assessed the impact of gut microbiota depletion, using an antibiotic cocktail, on aging and its impact on social behavior and the immune system. Indeed, microbiota depletion in aged mice eliminated the age-dependent deficits in social recognition. We further demonstrate that although age and gut microbiota depletion differently shape the peripheral immune response, aging induces an accumulation of T cells in the choroid plexus, that is partially blunted following microbiota depletion. Moreover, an untargeted metabolomic analysis revealed age-dependent alterations of cecal metabolites that are reshaped by gut microbiota depletion. Together, our results suggest that the aged gut microbiota can be specifically targeted to affect social deficits. These studies propel the need for future investigations of other non-antibiotic microbiota targeted interventions on age-related social deficits both in animal models and humans.

@article{
 title = {Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population},
 type = {article},
 year = {2023},
 pages = {601-610},
 volume = {28},
 month = {2},
 publisher = {Springer Nature},
 day = {1},
 id = {47679c57-7cd2-3d82-ab8d-4f2935872de9},
 created = {2025-07-07T13:25:47.115Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:29.887Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The impact of diet on the microbiota composition and the role of diet in supporting optimal mental health have received much attention in the last decade. However, whether whole dietary approaches can exert psychobiotic effects is largely understudied. Thus, we investigated the influence of a psychobiotic diet (high in prebiotic and fermented foods) on the microbial profile and function as well as on mental health outcomes in a healthy human population. Forty-five adults were randomized into either a psychobiotic (n = 24) or control (n = 21) diet for 4 weeks. Fecal microbiota composition and function was characterized using shotgun sequencing. Stress, overall health and diet were assessed using validated questionnaires. Metabolic profiling of plasma, urine and fecal samples was performed. Intervention with a psychobiotic diet resulted in reductions of perceived stress (32% in diet vs. 17% in control group), but not between groups. Similarly, biological marker of stress were not affected. Additionally, higher adherence to the diet resulted in stronger decreases in perceived stress. While the dietary intervention elicited only subtle changes in microbial composition and function, significant changes in the level of 40 specific fecal lipids and urinary tryptophan metabolites were observed. Lastly, microbial volatility was linked to greater changes in perceived stress scores in those on the psychobiotic diet. These results highlight that dietary approaches can be used to reduce perceived stress in a human cohort. Using microbiota-targeted diets to positively modulate gut-brain communication holds possibilities for the reduction of stress and stress-associated disorders, but additional research is warranted to investigate underlying mechanisms, including the role of the microbiota.},
 bibtype = {article},
 author = {Berding, Kirsten and Bastiaanssen, Thomaz F.S. and Moloney, Gerard M. and Boscaini, Serena and Strain, Conall R. and Anesi, Andrea and Long-Smith, Caitriona and Mattivi, Fulvio and Stanton, Catherine and Clarke, Gerard and Dinan, Timothy G. and Cryan, John F.},
 doi = {10.1038/s41380-022-01817-y},
 journal = {Molecular Psychiatry},
 number = {2}
}

The impact of diet on the microbiota composition and the role of diet in supporting optimal mental health have received much attention in the last decade. However, whether whole dietary approaches can exert psychobiotic effects is largely understudied. Thus, we investigated the influence of a psychobiotic diet (high in prebiotic and fermented foods) on the microbial profile and function as well as on mental health outcomes in a healthy human population. Forty-five adults were randomized into either a psychobiotic (n = 24) or control (n = 21) diet for 4 weeks. Fecal microbiota composition and function was characterized using shotgun sequencing. Stress, overall health and diet were assessed using validated questionnaires. Metabolic profiling of plasma, urine and fecal samples was performed. Intervention with a psychobiotic diet resulted in reductions of perceived stress (32% in diet vs. 17% in control group), but not between groups. Similarly, biological marker of stress were not affected. Additionally, higher adherence to the diet resulted in stronger decreases in perceived stress. While the dietary intervention elicited only subtle changes in microbial composition and function, significant changes in the level of 40 specific fecal lipids and urinary tryptophan metabolites were observed. Lastly, microbial volatility was linked to greater changes in perceived stress scores in those on the psychobiotic diet. These results highlight that dietary approaches can be used to reduce perceived stress in a human cohort. Using microbiota-targeted diets to positively modulate gut-brain communication holds possibilities for the reduction of stress and stress-associated disorders, but additional research is warranted to investigate underlying mechanisms, including the role of the microbiota.

@article{
 title = {Distinct Cerebrospinal Fluid Lipid Signature in Patients with Subarachnoid Hemorrhage-Induced Hydrocephalus},
 type = {article},
 year = {2023},
 keywords = {SAH,cerebrospinal fluid,lipidomics,mass spectrometry,posthemorrhagic hydrocephalus},
 volume = {11},
 month = {9},
 publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
 day = {1},
 id = {7e76599f-0d8b-396c-be29-5c44e1a2c626},
 created = {2025-07-07T13:25:47.444Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:30.208Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Patients with subarachnoid hemorrhage (SAH) may develop posthemorrhagic hydrocephalus (PHH), which is treated with surgical cerebrospinal fluid (CSF) diversion. This diversion is associated with risk of infection and shunt failure. Biomarkers for PHH etiology, CSF dynamics disturbances, and potentially subsequent shunt dependency are therefore in demand. With the recent demonstration of lipid-mediated CSF hypersecretion contributing to PHH, exploration of the CSF lipid signature in relation to brain pathology is of interest. Despite being a relatively new addition to the omic’s landscape, lipidomics are increasingly recognized as a tool for biomarker identification, as they provide a comprehensive overview of lipid profiles in biological systems. We here employ an untargeted mass spectroscopy-based platform and reveal the complete lipid profile of cisternal CSF from healthy control subjects and demonstrate its bimodal fluctuation with age. Various classes of lipids, in addition to select individual lipids, were elevated in the ventricular CSF obtained from patients with SAH during placement of an external ventricular drain. The lipidomic signature of the CSF in the patients with SAH suggests dysregulation of the lipids in the CSF in this patient group. Our data thereby reveal possible biomarkers present in a brain pathology with a hemorrhagic event, some of which could be potential future biomarkers for hypersecretion contributing to ventriculomegaly and thus pharmacological targets for pathologies involving disturbed CSF dynamics.},
 bibtype = {article},
 author = {Toft-Bertelsen, Trine L. and Andreassen, Søren Norge and Rostgaard, Nina and Olsen, Markus Harboe and Norager, Nicolas H. and Capion, Tenna and Juhler, Marianne and MacAulay, Nanna},
 doi = {10.3390/biomedicines11092360},
 journal = {Biomedicines},
 number = {9}
}

Patients with subarachnoid hemorrhage (SAH) may develop posthemorrhagic hydrocephalus (PHH), which is treated with surgical cerebrospinal fluid (CSF) diversion. This diversion is associated with risk of infection and shunt failure. Biomarkers for PHH etiology, CSF dynamics disturbances, and potentially subsequent shunt dependency are therefore in demand. With the recent demonstration of lipid-mediated CSF hypersecretion contributing to PHH, exploration of the CSF lipid signature in relation to brain pathology is of interest. Despite being a relatively new addition to the omic’s landscape, lipidomics are increasingly recognized as a tool for biomarker identification, as they provide a comprehensive overview of lipid profiles in biological systems. We here employ an untargeted mass spectroscopy-based platform and reveal the complete lipid profile of cisternal CSF from healthy control subjects and demonstrate its bimodal fluctuation with age. Various classes of lipids, in addition to select individual lipids, were elevated in the ventricular CSF obtained from patients with SAH during placement of an external ventricular drain. The lipidomic signature of the CSF in the patients with SAH suggests dysregulation of the lipids in the CSF in this patient group. Our data thereby reveal possible biomarkers present in a brain pathology with a hemorrhagic event, some of which could be potential future biomarkers for hypersecretion contributing to ventriculomegaly and thus pharmacological targets for pathologies involving disturbed CSF dynamics.

@article{
 title = {Obstructive sleep apnea was associated with the human gut microbiota composition and functional potential in the population-based Swedish CardioPulmonary bioImage Study (SCAPIS)},
 type = {article},
 year = {2023},
 websites = {https://doi.org/10.1016/j.chest.2023.03.010},
 publisher = {The Author(s)},
 id = {719e01f4-db56-378f-9373-59c10ca601d8},
 created = {2025-07-07T13:25:47.776Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:30.582Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Baldanzi, Gabriel and Sayols-Baixeras, Sergi and Theorell-Haglöw, Jenny and Dekkers, Koen F and Hammar, Ulf and Nguyen, Diem and Lin, Yi-Ting and Ahmad, Shafqat and Holm, Jacob Bak and Nielsen, Henrik Bjørn and Brunkwall, Louise and Benedict, Christian and Cedernaes, Jonathan and Koskiniemi, Sanna and Phillipson, Mia and Lind, Lars and Sundström, Johan and Bergström, Göran and Engström, Gunnar and Smith, J Gustav and Orho-Melander, Marju and Ärnlöv, Johan and Kennedy, Beatrice and Lindberg, Eva and Fall, Tove},
 doi = {10.1016/j.chest.2023.03.010},
 journal = {Chest},
 number = {April}
}

@article{
 title = {Identification of robust and generalizable biomarkers for microbiome-based stratification in lifestyle interventions},
 type = {article},
 year = {2023},
 keywords = {Gut microbiome,Lifestyle intervention,Machine learning,Microbiome dynamics,Resistance},
 volume = {11},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {134b53da-3151-3656-835b-69850cdf7437},
 created = {2025-10-30T12:05:02.939Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:20.931Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: A growing body of evidence suggests that the gut microbiota is strongly linked to general human health. Microbiome-directed interventions, such as diet and exercise, are acknowledged as a viable and achievable strategy for preventing disorders and improving human health. However, due to the significant inter-individual diversity of the gut microbiota between subjects, lifestyle recommendations are expected to have distinct and highly variable impacts to the microbiome structure. Results: Here, through a large-scale meta-analysis including 1448 shotgun metagenomics samples obtained longitudinally from 396 individuals during lifestyle studies, we revealed Bacteroides stercoris, Prevotella copri, and Bacteroides vulgatus as biomarkers of microbiota’s resistance to structural changes, and aromatic and non-aromatic amino acid biosynthesis as important regulator of microbiome dynamics. We established criteria for distinguishing between significant compositional changes from normal microbiota fluctuation and classified individuals based on their level of response. We further developed a machine learning model for predicting “responders” and “non-responders” independently of the type of intervention with an area under the curve of up to 0.86 in external validation cohorts of different ethnicities. Conclusions: We propose here that microbiome-based stratification is possible for identifying individuals with highly plastic or highly resistant microbial structures. Identifying subjects that will not respond to generalized lifestyle therapeutic interventions targeting the restructuring of gut microbiota is important to ensure that primary end-points of clinical studies are reached. [MediaObject not available: see fulltext.].},
 bibtype = {article},
 author = {Chen, Jiarui and Siliceo, Sara Leal and Ni, Yueqiong and Nielsen, Henrik B. and Xu, Aimin and Panagiotou, Gianni},
 doi = {10.1186/S40168-023-01604-Z},
 journal = {Microbiome},
 number = {1}
}

Background: A growing body of evidence suggests that the gut microbiota is strongly linked to general human health. Microbiome-directed interventions, such as diet and exercise, are acknowledged as a viable and achievable strategy for preventing disorders and improving human health. However, due to the significant inter-individual diversity of the gut microbiota between subjects, lifestyle recommendations are expected to have distinct and highly variable impacts to the microbiome structure. Results: Here, through a large-scale meta-analysis including 1448 shotgun metagenomics samples obtained longitudinally from 396 individuals during lifestyle studies, we revealed Bacteroides stercoris, Prevotella copri, and Bacteroides vulgatus as biomarkers of microbiota’s resistance to structural changes, and aromatic and non-aromatic amino acid biosynthesis as important regulator of microbiome dynamics. We established criteria for distinguishing between significant compositional changes from normal microbiota fluctuation and classified individuals based on their level of response. We further developed a machine learning model for predicting “responders” and “non-responders” independently of the type of intervention with an area under the curve of up to 0.86 in external validation cohorts of different ethnicities. Conclusions: We propose here that microbiome-based stratification is possible for identifying individuals with highly plastic or highly resistant microbial structures. Identifying subjects that will not respond to generalized lifestyle therapeutic interventions targeting the restructuring of gut microbiota is important to ensure that primary end-points of clinical studies are reached. [MediaObject not available: see fulltext.].

@article{
 title = {Neoepitope load, T cell signatures and PD-L2 as combined biomarker strategy for response to checkpoint inhibition immunotherapy},
 type = {article},
 year = {2023},
 keywords = {T cell signatures,biomarker,immune checkpoint inhibition,immunotherapy,neoepitopes,programmed cell death 1 ligand 2,tumor mutational burden},
 volume = {14},
 publisher = {Frontiers Media S.A.},
 id = {bc9cae16-3237-3270-86e9-8093a4073db7},
 created = {2025-10-30T12:05:03.009Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:10.717Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Immune checkpoint inhibition for the treatment of cancer has provided a breakthrough in oncology, and several new checkpoint inhibition pathways are currently being investigated regarding their potential to provide additional clinical benefit. However, only a fraction of patients respond to such treatment modalities, and there is an urgent need to identify biomarkers to rationally select patients that will benefit from treatment. In this study, we explore different tumor associated characteristics for their association with favorable clinical outcome in a diverse cohort of cancer patients treated with checkpoint inhibitors. We studied 29 patients in a basket trial comprising 12 different tumor types, treated with 10 different checkpoint inhibition regimens. Our analysis revealed that even across this diverse cohort, patients achieving clinical benefit had significantly higher neoepitope load, higher expression of T cell signatures, and higher PD-L2 expression, which also correlated with improved progression-free and overall survival. Importantly, the combination of biomarkers serves as a better predictor than each of the biomarkers alone. Basket trials are frequently used in modern immunotherapy trial design, and here we identify a set of biomarkers of potential relevance across multiple cancer types, allowing for the selection of patients that most likely will benefit from immune checkpoint inhibition.},
 bibtype = {article},
 author = {Borch, Annie and Bjerregaard, Anne Mette and Araujo Barbosa de Lima, Vinicius and Østrup, Olga and Yde, Christina Westmose and Eklund, Aron Charles and Mau-Sørensen, Morten and Barra, Carolina and Svane, Inge Marie and Nielsen, Finn Cilius and Funt, Samuel A. and Lassen, Ulrik and Hadrup, Sine Reker},
 doi = {10.3389/FGENE.2023.1058605},
 journal = {Frontiers in Genetics}
}

Immune checkpoint inhibition for the treatment of cancer has provided a breakthrough in oncology, and several new checkpoint inhibition pathways are currently being investigated regarding their potential to provide additional clinical benefit. However, only a fraction of patients respond to such treatment modalities, and there is an urgent need to identify biomarkers to rationally select patients that will benefit from treatment. In this study, we explore different tumor associated characteristics for their association with favorable clinical outcome in a diverse cohort of cancer patients treated with checkpoint inhibitors. We studied 29 patients in a basket trial comprising 12 different tumor types, treated with 10 different checkpoint inhibition regimens. Our analysis revealed that even across this diverse cohort, patients achieving clinical benefit had significantly higher neoepitope load, higher expression of T cell signatures, and higher PD-L2 expression, which also correlated with improved progression-free and overall survival. Importantly, the combination of biomarkers serves as a better predictor than each of the biomarkers alone. Basket trials are frequently used in modern immunotherapy trial design, and here we identify a set of biomarkers of potential relevance across multiple cancer types, allowing for the selection of patients that most likely will benefit from immune checkpoint inhibition.

@article{
 title = {Global within-species phylogenetics of sewage microbes suggest that local adaptation shapes geographical bacterial clustering},
 type = {article},
 year = {2023},
 volume = {6},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {7b8c83a2-7d20-3f1f-b158-71ec4ee75d56},
 created = {2025-10-30T12:05:03.031Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:11.753Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Most investigations of geographical within-species differences are limited to focusing on a single species. Here, we investigate global differences for multiple bacterial species using a dataset of 757 metagenomics sewage samples from 101 countries worldwide. The within-species variations were determined by performing genome reconstructions, and the analyses were expanded by gene focused approaches. Applying these methods, we recovered 3353 near complete (NC) metagenome assembled genomes (MAGs) encompassing 1439 different MAG species and found that within-species genomic variation was in 36% of the investigated species (12/33) coherent with regional separation. Additionally, we found that variation of organelle genes correlated less with geography compared to metabolic and membrane genes, suggesting that the global differences of these species are caused by regional environmental selection rather than dissemination limitations. From the combination of the large and globally distributed dataset and in-depth analysis, we present a wide investigation of global within-species phylogeny of sewage bacteria. The global differences found here emphasize the need for worldwide data sets when making global conclusions.},
 bibtype = {article},
 author = {Jespersen, Marie Louise and Munk, Patrick and Johansen, Joachim and Kaas, Rolf Sommer and Webel, Henry and Vigre, Håkan and Nielsen, Henrik Bjørn and Rasmussen, Simon and Aarestrup, Frank M.},
 doi = {10.1038/S42003-023-05083-8},
 journal = {Communications Biology},
 number = {1}
}

Most investigations of geographical within-species differences are limited to focusing on a single species. Here, we investigate global differences for multiple bacterial species using a dataset of 757 metagenomics sewage samples from 101 countries worldwide. The within-species variations were determined by performing genome reconstructions, and the analyses were expanded by gene focused approaches. Applying these methods, we recovered 3353 near complete (NC) metagenome assembled genomes (MAGs) encompassing 1439 different MAG species and found that within-species genomic variation was in 36% of the investigated species (12/33) coherent with regional separation. Additionally, we found that variation of organelle genes correlated less with geography compared to metabolic and membrane genes, suggesting that the global differences of these species are caused by regional environmental selection rather than dissemination limitations. From the combination of the large and globally distributed dataset and in-depth analysis, we present a wide investigation of global within-species phylogeny of sewage bacteria. The global differences found here emphasize the need for worldwide data sets when making global conclusions.

@article{
 title = {Infant Formula Supplemented with Five Human Milk Oligosaccharides Shifts the Fecal Microbiome of Formula-Fed Infants Closer to That of Breastfed Infants},
 type = {article},
 year = {2023},
 keywords = {aromatic lactic acids,bifidobacteria,breastfeeding,gut metabolic modules,gut microbiome development,human milk oligosaccharides,infant formula,infant-type bifidobacteria},
 volume = {15},
 month = {7},
 publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
 day = {1},
 id = {14bed0df-3c29-32a2-b3ea-bd697105c03d},
 created = {2025-10-30T12:05:03.036Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:19.373Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Breastmilk is the optimal source of infant nutrition, with short-term and long-term health benefits. Some of these benefits are mediated by human milk oligosaccharides (HMOs), a unique group of carbohydrates representing the third most abundant solid component of human milk. We performed the first clinical study on infant formula supplemented with five different HMOs (5HMO-mix), comprising 2′-fucosyllactose, 3-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose and 6′-sialyllactose at a natural total concentration of 5.75 g/L, and here report the analysis of the infant fecal microbiome. We found an increase in the relative abundance of bifidobacteria in the 5HMO-mix cohort compared with the formula-fed control, specifically affecting bifidobacteria that can produce aromatic lactic acids. 5HMO-mix influenced the microbial composition as early as Week 1, and the observed changes persisted to at least Week 16, including a relative decrease in species with opportunistic pathogenic strains down to the level observed in breastfed infants during the first 4 weeks. We further analyzed the functional potential of the microbiome and observed features shared between 5HMO-mix-supplemented and breastfed infants, such as a relative enrichment in mucus and tyrosine degradation, with the latter possibly being linked to the aromatic lactic acids. The 5HMO-mix supplement, therefore, shifts the infant fecal microbiome closer to that of breastfed infants.},
 bibtype = {article},
 author = {Holst, Andrea Q. and Myers, Pernille and Rodríguez-García, Paula and Hermes, Gerben D.A. and Melsaether, Cathrine and Baker, Adam and Jensen, Stina R. and Parschat, Katja},
 doi = {10.3390/NU15143087},
 journal = {Nutrients},
 number = {14}
}

Breastmilk is the optimal source of infant nutrition, with short-term and long-term health benefits. Some of these benefits are mediated by human milk oligosaccharides (HMOs), a unique group of carbohydrates representing the third most abundant solid component of human milk. We performed the first clinical study on infant formula supplemented with five different HMOs (5HMO-mix), comprising 2′-fucosyllactose, 3-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose and 6′-sialyllactose at a natural total concentration of 5.75 g/L, and here report the analysis of the infant fecal microbiome. We found an increase in the relative abundance of bifidobacteria in the 5HMO-mix cohort compared with the formula-fed control, specifically affecting bifidobacteria that can produce aromatic lactic acids. 5HMO-mix influenced the microbial composition as early as Week 1, and the observed changes persisted to at least Week 16, including a relative decrease in species with opportunistic pathogenic strains down to the level observed in breastfed infants during the first 4 weeks. We further analyzed the functional potential of the microbiome and observed features shared between 5HMO-mix-supplemented and breastfed infants, such as a relative enrichment in mucus and tyrosine degradation, with the latter possibly being linked to the aromatic lactic acids. The 5HMO-mix supplement, therefore, shifts the infant fecal microbiome closer to that of breastfed infants.

@article{
 title = {Safety, efficacy, and impact on gut microbial ecology of a Bifidobacterium longum subspecies infantis LMG11588 supplementation in healthy term infants: a randomized, double-blind, controlled trial in the Philippines},
 type = {article},
 year = {2023},
 keywords = {B. infantis LMG11588,Bifidobacterium-rich microbiota,autochthonous strains,infant growth,safety},
 volume = {10},
 publisher = {Frontiers Media SA},
 id = {385b7c85-7f52-39a0-a086-80b97cb2e768},
 created = {2025-10-30T12:05:03.060Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:15.805Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction: Bifidobacterium longum subspecies infantis (B. infantis) may play a key role in infant gut development. This trial evaluated safety, tolerability, and efficacy of B. infantis LMG11588 supplementation. Methods: This randomized, placebo-controlled, double-blind study conducted in the Philippines included healthy breastfed and/or formula-fed infants (14–21 days old) randomized for 8 weeks to a control group (CG; n = 77), or any of two B. infantis experimental groups (EGs): low (Lo-EG; 1*108 CFU/day; n = 75) or high dose (Hi-EG; 1.8*1010 CFU/day; n = 76). Primary endpoint was weight gain; secondary endpoints included stooling patterns, gastrointestinal symptoms, adverse events, fecal microbiome, biomarkers, pH, and organic acids. Results: Non-inferiority in weight gain was demonstrated for Hi-EG and Lo-EG vs. CG. Overall, probiotic supplementation promoted mushy-soft stools, fewer regurgitation episodes, and increased fecal acetate production, which was more pronounced in the exclusively breastfed infants (EBF) and positively correlated with B. infantis abundance. In EBF, fecal pro-inflammatory cytokines (IL-1 beta, IL-8) were reduced. Strain-level metagenomic analysis allowed attributing the increased abundance of B. infantis in EGs versus CG, to LMG11588 probiotic colonization. Colonization by autochthonous B. infantis strains was similar between groups. Discussion: B. infantis LMG11588 supplementation was associated with normal infant growth, was safe and well-tolerated and promoted a Bifidobacterium-rich microbiota driven by B. infantis LMG11588 colonization without disturbing the natural dispersal of autochthonous B. infantis strains. In EBF, supplementation stimulated microbial metabolic activity and beneficially modulated enteric inflammation.},
 bibtype = {article},
 author = {Capeding, Maria Rosario Z. and Phee, Loudhie Cyd M. and Ming, Chang and Noti, Mario and Vidal, Karine and Le Carrou, Gilles and Frézal, A. and Moll, Janne Marie and Vogt, Josef Korbinian and Myers, Pernille Neve and Nielsen, Bjørn Henrik and Boulangé, Claire L. and Samuel, Tinu Mary and Berger, Bernard and Cercamondi, Colin Ivano},
 doi = {10.3389/FNUT.2023.1319873},
 journal = {Frontiers in Nutrition}
}

Introduction: Bifidobacterium longum subspecies infantis (B. infantis) may play a key role in infant gut development. This trial evaluated safety, tolerability, and efficacy of B. infantis LMG11588 supplementation. Methods: This randomized, placebo-controlled, double-blind study conducted in the Philippines included healthy breastfed and/or formula-fed infants (14–21 days old) randomized for 8 weeks to a control group (CG; n = 77), or any of two B. infantis experimental groups (EGs): low (Lo-EG; 1*108 CFU/day; n = 75) or high dose (Hi-EG; 1.8*1010 CFU/day; n = 76). Primary endpoint was weight gain; secondary endpoints included stooling patterns, gastrointestinal symptoms, adverse events, fecal microbiome, biomarkers, pH, and organic acids. Results: Non-inferiority in weight gain was demonstrated for Hi-EG and Lo-EG vs. CG. Overall, probiotic supplementation promoted mushy-soft stools, fewer regurgitation episodes, and increased fecal acetate production, which was more pronounced in the exclusively breastfed infants (EBF) and positively correlated with B. infantis abundance. In EBF, fecal pro-inflammatory cytokines (IL-1 beta, IL-8) were reduced. Strain-level metagenomic analysis allowed attributing the increased abundance of B. infantis in EGs versus CG, to LMG11588 probiotic colonization. Colonization by autochthonous B. infantis strains was similar between groups. Discussion: B. infantis LMG11588 supplementation was associated with normal infant growth, was safe and well-tolerated and promoted a Bifidobacterium-rich microbiota driven by B. infantis LMG11588 colonization without disturbing the natural dispersal of autochthonous B. infantis strains. In EBF, supplementation stimulated microbial metabolic activity and beneficially modulated enteric inflammation.

@article{
 title = {Identification of representative species-specific genes for abundance measurements},
 type = {article},
 year = {2023},
 volume = {3},
 publisher = {Oxford University Press},
 id = {99fcb55c-42f9-390f-a205-2b2d193c5ac3},
 created = {2025-10-30T12:05:03.068Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:11.015Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Motivation: Metagenomic binning facilitates the reconstruction of genomes and identification of Metagenomic Species Pan-genomes or Metagenomic Assembled Genomes. We propose a method for identifying a set of de novo representative genes, termed signature genes, which can be used to measure the relative abundance and used as markers of each metagenomic species with high accuracy. Results: An initial set of the 100 genes that correlate with the median gene abundance profile of the entity is selected. A variant of the coupon collector's problem was utilized to evaluate the probability of identifying a certain number of unique genes in a sample. This allows us to reject the abundance measurements of strains exhibiting a significantly skewed gene representation. A rank-based negative binomial model is employed to assess the performance of different gene sets across a large set of samples, facilitating identification of an optimal signature gene set for the entity. When benchmarked the method on a synthetic gene catalog, our optimized signature gene sets estimate relative abundance significantly closer to the true relative abundance compared to the starting gene sets extracted from the metagenomic species. The method was able to replicate results from a study with real data and identify around three times as many metagenomic entities.},
 bibtype = {article},
 author = {Zachariasen, Trine and Petersen, Anders Østergaard and Brejnrod, Asker and Vestergaard, Gisle Alberg and Eklund, Aron and Nielsen, Henrik Bjørn},
 doi = {10.1093/BIOADV/VBAD060},
 journal = {Bioinformatics Advances},
 number = {1}
}

Motivation: Metagenomic binning facilitates the reconstruction of genomes and identification of Metagenomic Species Pan-genomes or Metagenomic Assembled Genomes. We propose a method for identifying a set of de novo representative genes, termed signature genes, which can be used to measure the relative abundance and used as markers of each metagenomic species with high accuracy. Results: An initial set of the 100 genes that correlate with the median gene abundance profile of the entity is selected. A variant of the coupon collector's problem was utilized to evaluate the probability of identifying a certain number of unique genes in a sample. This allows us to reject the abundance measurements of strains exhibiting a significantly skewed gene representation. A rank-based negative binomial model is employed to assess the performance of different gene sets across a large set of samples, facilitating identification of an optimal signature gene set for the entity. When benchmarked the method on a synthetic gene catalog, our optimized signature gene sets estimate relative abundance significantly closer to the true relative abundance compared to the starting gene sets extracted from the metagenomic species. The method was able to replicate results from a study with real data and identify around three times as many metagenomic entities.

@article{
 title = {Reversible aberrancies in gut microbiome of moderate and late preterm infants: results from a randomized, controlled trial},
 type = {article},
 year = {2023},
 keywords = {Bifidobacteria,gut microbiome,late preterm,moderate preterm,prebiotics,preterm,probiotics},
 volume = {15},
 publisher = {Taylor and Francis Ltd.},
 id = {e91f0c37-6e47-36ce-9b91-c33c1bf560f4},
 created = {2025-10-30T12:05:03.074Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.074Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The aim of this study was to obtain insight into the composition and function of the deviant gut microbiome throughout infancy in children born moderately and late preterm and their response to microbiome modulation. We characterized the longitudinal development of the gut microbiome from birth to the age of 12 months by metagenomic sequencing in 43 moderate and late preterm children participating in a randomized, controlled trial (ClinicalTrials.gov/no.NCT00167700) assessing the impact of a probiotic (Lactobacillus rhamnosus GG, ATCC 53,103, currently Lacticaseibacillus rhamnosus GG) and a prebiotic (galacto-oligosaccharide and polydextrose mixture, 1:1) intervention as compared to a placebo administered from 3 to 60 days of life. In addition, 9 full-term, vaginally delivered, breast-fed infants, who remained healthy long-term were included as references. Significant differences in taxonomy, but not in functional potential, were found when comparing the gut microbiome composition of preterm and full-term infants during the first month of life. However, the gut microbiome of preterm infants resembled that of full-term infants by 6 months age. Probiotic and prebiotic treatments were found to mitigate the shift in the microbiome of preterm infants by accelerating Bifidobacteria-dominated gut microbiome in beta diversity analysis. This study provides intriguing information regarding the establishment of the gut microbiome in children born moderately and late preterm, representing the majority of children born preterm. Specific pro- and prebiotics may reverse the proinflammatory gut microbiome composition during the vulnerable period, when the microbiome is low in resilience and susceptible to environmental exposure and simultaneously promotes immunological and metabolic maturation.},
 bibtype = {article},
 author = {Luoto, Raakel and Pärtty, Anna and Vogt, Josef K. and Rautava, Samuli and Isolauri, Erika},
 doi = {10.1080/19490976.2023.2283913},
 journal = {Gut Microbes},
 number = {2}
}

The aim of this study was to obtain insight into the composition and function of the deviant gut microbiome throughout infancy in children born moderately and late preterm and their response to microbiome modulation. We characterized the longitudinal development of the gut microbiome from birth to the age of 12 months by metagenomic sequencing in 43 moderate and late preterm children participating in a randomized, controlled trial (ClinicalTrials.gov/no.NCT00167700) assessing the impact of a probiotic (Lactobacillus rhamnosus GG, ATCC 53,103, currently Lacticaseibacillus rhamnosus GG) and a prebiotic (galacto-oligosaccharide and polydextrose mixture, 1:1) intervention as compared to a placebo administered from 3 to 60 days of life. In addition, 9 full-term, vaginally delivered, breast-fed infants, who remained healthy long-term were included as references. Significant differences in taxonomy, but not in functional potential, were found when comparing the gut microbiome composition of preterm and full-term infants during the first month of life. However, the gut microbiome of preterm infants resembled that of full-term infants by 6 months age. Probiotic and prebiotic treatments were found to mitigate the shift in the microbiome of preterm infants by accelerating Bifidobacteria-dominated gut microbiome in beta diversity analysis. This study provides intriguing information regarding the establishment of the gut microbiome in children born moderately and late preterm, representing the majority of children born preterm. Specific pro- and prebiotics may reverse the proinflammatory gut microbiome composition during the vulnerable period, when the microbiome is low in resilience and susceptible to environmental exposure and simultaneously promotes immunological and metabolic maturation.

@article{
 title = {Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort},
 type = {article},
 year = {2023},
 keywords = {Streptococcus,atherosclerosis,gastrointestinal microbiome,metagenomics,tomography},
 pages = {459-472},
 volume = {148},
 month = {8},
 publisher = {Lippincott Williams and Wilkins},
 day = {8},
 id = {21c4ff1d-b6c5-3ebb-9f33-4bd826a44c01},
 created = {2025-10-30T12:05:03.075Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:10.926Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates. Methods: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva. Results: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score. Conclusions: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.},
 bibtype = {article},
 author = {Sayols-Baixeras, Sergi and Dekkers, Koen F. and Baldanzi, Gabriel and Jönsson, Daniel and Hammar, Ulf and Lin, Yi Ting and Ahmad, Shafqat and Nguyen, Diem and Varotsis, Georgios and Pita, Sara and Nielsen, Nynne and Eklund, Aron C. and Holm, Jacob B. and Nielsen, H. Bjørn and Ericson, Ulrika and Brunkwall, Louise and Ottosson, Filip and Larsson, Anna and Ericson, Dan and Klinge, Björn and Nilsson, Peter M. and Malinovschi, Andrei and Lind, Lars and Bergström, Göran and Sundström, Johan and Ärnlöv, Johan and Engström, Gunnar and Smith, J. Gustav and Orho-Melander, Marju and Fall, Tove},
 doi = {10.1161/CIRCULATIONAHA.123.063914},
 journal = {Circulation},
 number = {6}
}

Background: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates. Methods: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva. Results: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score. Conclusions: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.

@article{
 title = {Results of the 2020 Genomic Proficiency Test for the network of European Union Reference Laboratory for Antimicrobial Resistance assessing whole-genome-sequencing capacities},
 type = {article},
 year = {2023},
 keywords = {Genomic Proficiency Test,Pathogenic bacteria,Quality control,Short-read sequencing,Statistical comparison,Whole Genome Sequencing},
 volume = {9},
 publisher = {Microbiology Society},
 id = {a484d213-ec1d-30a4-a1d0-317457cb3339},
 created = {2025-10-30T12:05:03.107Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.107Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The global surveillance and outbreak investigation of antimicrobial resistance (AMR) is amidst a paradigm shift from traditional biology to bioinformatics. This is due to developments in whole-genome-sequencing (WGS) technologies, bioinformatics tools, and reduced costs. The increased use of WGS is accompanied by challenges such as standardization, quality control (QC), and data sharing. Thus, there is global need for inter-laboratory WGS proficiency test (PT) schemes to evaluate laboratories' capacity to produce reliable genomic data. Here, we present the results of the first iteration of the Genomic PT (GPT) organized by the Global Capacity Building Group at the Technical University of Denmark in 2020. Participating laboratories sequenced two isolates and corresponding DNA of Salmonella enterica, Escherichia coli and Campylobacter coli, using WGS methodologies routinely employed at their laboratories. The participants' ability to obtain consistently good-quality WGS data was assessed based on several QC WGS metrics. A total of 21 laboratories from 21 European countries submitted WGS and meta-data. Most delivered high-quality sequence data with only two laboratories identified as overall underperforming. The QC metrics, N50 and number of contigs, were identified as good indicators for high-sequencing quality. We propose QC thresholds for N50 greater than 20 000 and 25 000 for Campylobacter coli and Escherichia coli, respectively, and number of contigs >200 bp greater than 225, 265 and 100 for Salmonella enterica, Escherichia coli and Campylobacter coli, respectively. The GPT2020 results confirm the importance of systematic QC procedures, ensuring the submission of reliable WGS data for surveillance and outbreak investigation to meet the requirements of the paradigm shift in methodology.},
 bibtype = {article},
 author = {Kristensen, Thea and Sørensen, Lauge Holm and Pedersen, Susanne Karlsmose and Jensen, Jacob Dyring and Mordhorst, Hanne and Lacy-Roberts, Niamh and Lukjancenko, Oksana and Luo, Yan and Hoffmann, Maria and Hendriksen, Rene S.},
 doi = {10.1099/MGEN.0.001076},
 journal = {Microbial Genomics},
 number = {8}
}

The global surveillance and outbreak investigation of antimicrobial resistance (AMR) is amidst a paradigm shift from traditional biology to bioinformatics. This is due to developments in whole-genome-sequencing (WGS) technologies, bioinformatics tools, and reduced costs. The increased use of WGS is accompanied by challenges such as standardization, quality control (QC), and data sharing. Thus, there is global need for inter-laboratory WGS proficiency test (PT) schemes to evaluate laboratories' capacity to produce reliable genomic data. Here, we present the results of the first iteration of the Genomic PT (GPT) organized by the Global Capacity Building Group at the Technical University of Denmark in 2020. Participating laboratories sequenced two isolates and corresponding DNA of Salmonella enterica, Escherichia coli and Campylobacter coli, using WGS methodologies routinely employed at their laboratories. The participants' ability to obtain consistently good-quality WGS data was assessed based on several QC WGS metrics. A total of 21 laboratories from 21 European countries submitted WGS and meta-data. Most delivered high-quality sequence data with only two laboratories identified as overall underperforming. The QC metrics, N50 and number of contigs, were identified as good indicators for high-sequencing quality. We propose QC thresholds for N50 greater than 20 000 and 25 000 for Campylobacter coli and Escherichia coli, respectively, and number of contigs >200 bp greater than 225, 265 and 100 for Salmonella enterica, Escherichia coli and Campylobacter coli, respectively. The GPT2020 results confirm the importance of systematic QC procedures, ensuring the submission of reliable WGS data for surveillance and outbreak investigation to meet the requirements of the paradigm shift in methodology.

@article{
 title = {OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study},
 type = {article},
 year = {2023},
 keywords = {OSA,epidemiology,microbiota},
 pages = {503-516},
 volume = {164},
 month = {8},
 publisher = {Elsevier Inc.},
 day = {1},
 id = {e0cd25ea-8e7e-31e5-86c7-9bc263b4443d},
 created = {2025-10-30T12:05:03.110Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:06.363Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism. Research Question: Does OSA in adults associate with the composition and functional potential of the human gut microbiota? Study Design and Methods: We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register. Results: We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively. Interpretation: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.},
 bibtype = {article},
 author = {Baldanzi, Gabriel and Sayols-Baixeras, Sergi and Theorell-Haglöw, Jenny and Dekkers, Koen F. and Hammar, Ulf and Nguyen, Diem and Lin, Yi Ting and Ahmad, Shafqat and Holm, Jacob Bak and Nielsen, Henrik Bjørn and Brunkwall, Louise and Benedict, Christian and Cedernaes, Jonathan and Koskiniemi, Sanna and Phillipson, Mia and Lind, Lars and Sundström, Johan and Bergström, Göran and Engström, Gunnar and Smith, J. Gustav and Orho-Melander, Marju and Ärnlöv, Johan and Kennedy, Beatrice and Lindberg, Eva and Fall, Tove},
 doi = {10.1016/J.CHEST.2023.03.010},
 journal = {Chest},
 number = {2}
}

Background: OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism. Research Question: Does OSA in adults associate with the composition and functional potential of the human gut microbiota? Study Design and Methods: We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register. Results: We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively. Interpretation: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.

@article{
 title = {Reduced Skin Microbiome Diversity in Infancy Is Associated with Increased Risk of Atopic Dermatitis in High-Risk Children},
 type = {article},
 year = {2023},
 pages = {2030-2038.e6},
 volume = {143},
 month = {10},
 publisher = {Elsevier B.V.},
 day = {1},
 id = {304bf228-17e2-329a-bd44-1864ea0c570a},
 created = {2025-10-30T12:05:03.157Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:06.241Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {It is currently unknown whether alterations in the skin microbiome exist before development of atopic dermatitis (AD). In this prospective Danish birth cohort of 300 children, we examined whether skin microbiome alterations during the first 2 months of life were associated with an increased risk of AD in the first 2 years and its severity after adjustment for environmental factors and selected skin chemokine and natural moisturizing factor levels. We found no overall association between the skin microbiome at birth and age 2 months and AD during the first 2 years of life. However, when restricting the analysis to children with at least one parent with atopy, a lower alpha diversity at age 2 months was associated with an increased risk of AD (adjusted hazard ratio = 1.7, 95% confidence interval = 1.1–2.6). We observed a stronger association in children where both parents had atopy (adjusted hazard ratio = 4.4, 95% confidence interval = 1.1–18.2). The putative pathogenic role of changes in the skin microbiome on AD risk remains uncertain but may play a role in those with an atopic predisposition.},
 bibtype = {article},
 author = {Halling, Anne Sofie and Fritz, Blaine Gabriel and Gerner, Trine and Rinnov, Maria Rasmussen and Bay, Lene and Knudgaard, Mette Hjorslev and Ravn, Nina Haarup and Trautner, Simon and Ruge, Iben Frier and Olesen, Caroline and Díiaz-Pinées Cort, Isabel and Skov, Lone and Sørensen, Nikolaj and Møller Rønnstad, Amalie Thorsti and Thomsen, Simon F. and Egeberg, Alexander and Jakasa, Ivone and Kezic, Sanja and Bjarnsholt, Thomas and Thyssen, Jacob P.},
 doi = {10.1016/J.JID.2023.03.1682},
 journal = {Journal of Investigative Dermatology},
 number = {10}
}

It is currently unknown whether alterations in the skin microbiome exist before development of atopic dermatitis (AD). In this prospective Danish birth cohort of 300 children, we examined whether skin microbiome alterations during the first 2 months of life were associated with an increased risk of AD in the first 2 years and its severity after adjustment for environmental factors and selected skin chemokine and natural moisturizing factor levels. We found no overall association between the skin microbiome at birth and age 2 months and AD during the first 2 years of life. However, when restricting the analysis to children with at least one parent with atopy, a lower alpha diversity at age 2 months was associated with an increased risk of AD (adjusted hazard ratio = 1.7, 95% confidence interval = 1.1–2.6). We observed a stronger association in children where both parents had atopy (adjusted hazard ratio = 4.4, 95% confidence interval = 1.1–18.2). The putative pathogenic role of changes in the skin microbiome on AD risk remains uncertain but may play a role in those with an atopic predisposition.

@article{
 title = {An Extensively Hydrolyzed Formula Supplemented with Two Human Milk Oligosaccharides Modifies the Fecal Microbiome and Metabolome in Infants with Cow’s Milk Protein Allergy},
 type = {article},
 year = {2023},
 keywords = {amino acids,bile acids,fecal community type,human milk oligosaccharides,metabolomics,metagenomics,microbiome,short-chain fatty acids},
 volume = {24},
 month = {7},
 publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
 day = {1},
 id = {bd5927d8-fc3e-310e-9e9a-eea271802036},
 created = {2025-10-30T12:05:03.299Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:18.259Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Cow’s milk protein allergy (CMPA) is a prevalent food allergy among infants and young children. We conducted a randomized, multicenter intervention study involving 194 non-breastfed infants with CMPA until 12 months of age (clinical trial registration: NCT03085134). One exploratory objective was to assess the effects of a whey-based extensively hydrolyzed formula (EHF) supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT) on the fecal microbiome and metabolome in this population. Thus, fecal samples were collected at baseline, 1 and 3 months from enrollment, as well as at 12 months of age. Human milk oligosaccharides (HMO) supplementation led to the enrichment of bifidobacteria in the gut microbiome and delayed the shift of the microbiome composition toward an adult-like pattern. We identified specific HMO-mediated changes in fecal amino acid degradation and bile acid conjugation, particularly in infants commencing the HMO-supplemented formula before the age of three months. Thus, HMO supplementation partially corrected the dysbiosis commonly observed in infants with CMPA. Further investigation is necessary to determine the clinical significance of these findings in terms of a reduced incidence of respiratory infections and other potential health benefits.},
 bibtype = {article},
 author = {Boulangé, Claire L. and Pedersen, Helle K. and Martin, Francois Pierre and Siegwald, Léa and Pallejà Caro, Albert and Eklund, Aron C. and Jia, Wei and Zhang, Huizhen and Berger, Bernard and Sprenger, Norbert and Heine, Ralf G.},
 doi = {10.3390/IJMS241411422},
 journal = {International Journal of Molecular Sciences},
 number = {14}
}

Cow’s milk protein allergy (CMPA) is a prevalent food allergy among infants and young children. We conducted a randomized, multicenter intervention study involving 194 non-breastfed infants with CMPA until 12 months of age (clinical trial registration: NCT03085134). One exploratory objective was to assess the effects of a whey-based extensively hydrolyzed formula (EHF) supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT) on the fecal microbiome and metabolome in this population. Thus, fecal samples were collected at baseline, 1 and 3 months from enrollment, as well as at 12 months of age. Human milk oligosaccharides (HMO) supplementation led to the enrichment of bifidobacteria in the gut microbiome and delayed the shift of the microbiome composition toward an adult-like pattern. We identified specific HMO-mediated changes in fecal amino acid degradation and bile acid conjugation, particularly in infants commencing the HMO-supplemented formula before the age of three months. Thus, HMO supplementation partially corrected the dysbiosis commonly observed in infants with CMPA. Further investigation is necessary to determine the clinical significance of these findings in terms of a reduced incidence of respiratory infections and other potential health benefits.

@article{
 title = {Inhibition of carnitine palmitoyl-transferase 1 is a potential target in a mouse model of Parkinson's disease.},
 type = {article},
 year = {2023},
 pages = {6},
 volume = {9},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/36681683,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9867753},
 month = {1},
 publisher = {Nature Research},
 day = {21},
 id = {e642b7cb-0f11-306f-bedf-324ed6e4b0b5},
 created = {2025-10-30T12:18:14.095Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:18:18.055Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Glucose metabolism is dysregulated in Parkinson's disease (PD) causing a shift toward the metabolism of lipids. Carnitine palmitoyl-transferase 1A (CPT1A) regulates the key step in the metabolism of long-chain fatty acids. The aim of this study is to evaluate the effect of downregulating CPT1, either genetically with a Cpt1a P479L mutation or medicinally on PD using chronic rotenone mouse models using C57Bl/6J and Park2 knockout mice. We show that Cpt1a P479L mutant mice are resistant to rotenone-induced PD, and that inhibition of CPT1 is capable of restoring neurological function, normal glucose metabolism, and alleviate markers of PD in the midbrain. Furthermore, we show that downregulation of lipid metabolism via CPT1 alleviates pathological motor and non-motor behavior, oxidative stress, and disrupted glucose homeostasis in Park2 knockout mice. Finally, we confirm that rotenone induces gut dysbiosis in C57Bl/6J and, for the first time, in Park2 knockout mice. We show that this dysbiosis is alleviated by the downregulation of the lipid metabolism via CPT1.},
 bibtype = {article},
 author = {Trabjerg, Michael Sloth and Andersen, Dennis Christian and Huntjens, Pam and Mørk, Kasper and Warming, Nikolaj and Kullab, Ulla Bismark and Skjønnemand, Marie-Louise Nibelius and Oklinski, Michal Krystian and Oklinski, Kirsten Egelund and Bolther, Luise and Kroese, Lona J and Pritchard, Colin E J and Huijbers, Ivo J and Corthals, Angelique and Søndergaard, Mads Toft and Kjeldal, Henrik Bech and Pedersen, Cecilie Fjord Morre and Nieland, John Dirk Vestergaard},
 doi = {10.1038/s41531-023-00450-y},
 journal = {NPJ Parkinson's disease},
 number = {1}
}

Glucose metabolism is dysregulated in Parkinson's disease (PD) causing a shift toward the metabolism of lipids. Carnitine palmitoyl-transferase 1A (CPT1A) regulates the key step in the metabolism of long-chain fatty acids. The aim of this study is to evaluate the effect of downregulating CPT1, either genetically with a Cpt1a P479L mutation or medicinally on PD using chronic rotenone mouse models using C57Bl/6J and Park2 knockout mice. We show that Cpt1a P479L mutant mice are resistant to rotenone-induced PD, and that inhibition of CPT1 is capable of restoring neurological function, normal glucose metabolism, and alleviate markers of PD in the midbrain. Furthermore, we show that downregulation of lipid metabolism via CPT1 alleviates pathological motor and non-motor behavior, oxidative stress, and disrupted glucose homeostasis in Park2 knockout mice. Finally, we confirm that rotenone induces gut dysbiosis in C57Bl/6J and, for the first time, in Park2 knockout mice. We show that this dysbiosis is alleviated by the downregulation of the lipid metabolism via CPT1.

@article{
 title = {Bridging preclinical and clinical gut microbiota research using the ex vivo SIFR® technology.},
 type = {article},
 year = {2023},
 keywords = {SIFR®,ex vivo,gut,microbiota,prebiotic},
 pages = {1131662},
 volume = {14},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/37187538,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC10178071},
 publisher = {Frontiers Media S.A.},
 id = {40664a36-e666-3326-89ca-dffd8868f6b7},
 created = {2025-10-30T12:26:00.885Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.885Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {INTRODUCTION While modulation of the human adult gut microbiota is a trending strategy to improve health, the underlying mechanisms are poorly understood. METHODS This study aimed to assess the predictive value of the ex vivo, reactor-based, high-throughput SIFR® (Systemic Intestinal Fermentation Research) technology for clinical findings using three structurally different prebiotics [inulin (IN), resistant dextrin (RD) and 2'-fucosyllactose (2'FL)]. RESULTS The key finding was that data obtained within 1-2 days were predictive for clinical findings upon repeated prebiotic intake over weeks: among hundreds of microbes, IN stimulated Bifidobacteriaceae, RD boosted Parabacteroides distasonis, while 2'FL specifically increased Bifidobacterium adolescentis and Anaerobutyricum hallii. In line with metabolic capabilities of these taxa, specific SCFA (short-chain fatty acids) were produced thus providing insights that cannot be obtained in vivo where such metabolites are rapidly absorbed. Further, in contrast to using single or pooled fecal microbiota (approaches used to circumvent low throughput of conventional models), working with 6 individual fecal microbiota enabled correlations that support mechanistic insights. Moreover, quantitative sequencing removed the noise caused by markedly increased cell densities upon prebiotic treatment, thus allowing to even rectify conclusions of previous clinical trials related to the tentative selectivity by which prebiotics modulate the gut microbiota. Counterintuitively, not the high but rather the low selectivity of IN caused only a limited number of taxa to be significantly affected. Finally, while a mucosal microbiota (enriched with Lachnospiraceae) can be integrated, other technical aspects of the SIFR® technology are a high technical reproducibility, and most importantly, a sustained similarity between the ex vivo and original in vivo microbiota. DISCUSSION By accurately predicting in vivo results within days, the SIFR® technology can help bridge the so-called "Valley of Death" between preclinical and clinical research. Facilitating development of test products with better understanding of their mode of action could dramatically increase success rate of microbiome modulating clinical trials.Graphical Abstract.},
 bibtype = {article},
 author = {Van den Abbeele, Pieter and Deyaert, Stef and Thabuis, Clémentine and Perreau, Caroline and Bajic, Danica and Wintergerst, Eva and Joossens, Marie and Firrman, Jenni and Walsh, Dana and Baudot, Aurélien},
 doi = {10.3389/fmicb.2023.1131662},
 journal = {Frontiers in microbiology}
}

INTRODUCTION While modulation of the human adult gut microbiota is a trending strategy to improve health, the underlying mechanisms are poorly understood. METHODS This study aimed to assess the predictive value of the ex vivo, reactor-based, high-throughput SIFR® (Systemic Intestinal Fermentation Research) technology for clinical findings using three structurally different prebiotics [inulin (IN), resistant dextrin (RD) and 2'-fucosyllactose (2'FL)]. RESULTS The key finding was that data obtained within 1-2 days were predictive for clinical findings upon repeated prebiotic intake over weeks: among hundreds of microbes, IN stimulated Bifidobacteriaceae, RD boosted Parabacteroides distasonis, while 2'FL specifically increased Bifidobacterium adolescentis and Anaerobutyricum hallii. In line with metabolic capabilities of these taxa, specific SCFA (short-chain fatty acids) were produced thus providing insights that cannot be obtained in vivo where such metabolites are rapidly absorbed. Further, in contrast to using single or pooled fecal microbiota (approaches used to circumvent low throughput of conventional models), working with 6 individual fecal microbiota enabled correlations that support mechanistic insights. Moreover, quantitative sequencing removed the noise caused by markedly increased cell densities upon prebiotic treatment, thus allowing to even rectify conclusions of previous clinical trials related to the tentative selectivity by which prebiotics modulate the gut microbiota. Counterintuitively, not the high but rather the low selectivity of IN caused only a limited number of taxa to be significantly affected. Finally, while a mucosal microbiota (enriched with Lachnospiraceae) can be integrated, other technical aspects of the SIFR® technology are a high technical reproducibility, and most importantly, a sustained similarity between the ex vivo and original in vivo microbiota. DISCUSSION By accurately predicting in vivo results within days, the SIFR® technology can help bridge the so-called "Valley of Death" between preclinical and clinical research. Facilitating development of test products with better understanding of their mode of action could dramatically increase success rate of microbiome modulating clinical trials.Graphical Abstract.

@article{
 title = {Microbiome Analysis of Organic and Conventional Chickens Processed Using Whole Carcass Enrichment and Rinse Methods},
 type = {article},
 year = {2023},
 keywords = {16S rRNA sequencing,Chicken,Diversity,Microbiome,Organic,Pathogen},
 volume = {86},
 month = {11},
 publisher = {Elsevier B.V.},
 day = {1},
 id = {7b4a7d4c-45b3-3b51-ad11-ab3a142ec302},
 created = {2025-10-30T12:26:00.909Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:03.500Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Investigating the chicken microbiome is important to establish control measures for pathogens to protect consumers. This study aimed at evaluating the comparative efficiency of human pathogen detection through 16S rRNA sequencing of organic and conventional chickens processed using whole carcass enrichment (WCE) and rinse (WCR) methods. Organic and conventional whole broiler carcasses (n = 31) were vigorously shaken with 500 mL buffered peptone water (BPW). For the rinse method, a 30 mL aliquot was mixed with 30 mL of BPW. The rest of the sample, including the carcass, was used for the enrichment method. All samples were incubated at 37°C for 24 h. The samples were divided into five groups [Negative Control: only BPW without chicken (n = 5), Organic-Rinsed (n = 7), -Enriched (n = 8), Conventional-Rinsed (n = 7), and -Enriched (n = 9)]. Fifty milliliters of each sample were subjected to DNA extraction followed by 16S rRNA sequencing. Proteobacteria and Firmicutes predominated the microbiota of both conventional and organic chickens, followed by low abundances of Bacteroidetes and Fusobacterium. While the abundance of Proteobacteria and Firmicutes remained unchanged in organic chicken irrespective of the methods used, a noticeable shift in the Proteobacteria and Firmicutes ratio (59%:39% in rinsed to 38%:60% in enriched) was observed in conventional chicken. Furthermore, the choice of method did not yield any differences in Abundance-Based Coverage Estimator, and Jackknife, among conventional and organic chickens but resulted in a statistically significant difference in the Shannon, Simpson, Chao1, and phylogenetic diversity indices (p < 0.05). The relative abundance of Salmonella and Campylobacter was less than 0.1%. The results suggested the WCE method provides a broad range of information on the chicken microbiome.},
 bibtype = {article},
 author = {Punchihewage-Don, Anuradha J. and Hasan, Nur A. and Rashed, Shah M. and Parveen, Salina},
 doi = {10.1016/j.jfp.2023.100176},
 journal = {Journal of Food Protection},
 number = {11}
}

Investigating the chicken microbiome is important to establish control measures for pathogens to protect consumers. This study aimed at evaluating the comparative efficiency of human pathogen detection through 16S rRNA sequencing of organic and conventional chickens processed using whole carcass enrichment (WCE) and rinse (WCR) methods. Organic and conventional whole broiler carcasses (n = 31) were vigorously shaken with 500 mL buffered peptone water (BPW). For the rinse method, a 30 mL aliquot was mixed with 30 mL of BPW. The rest of the sample, including the carcass, was used for the enrichment method. All samples were incubated at 37°C for 24 h. The samples were divided into five groups [Negative Control: only BPW without chicken (n = 5), Organic-Rinsed (n = 7), -Enriched (n = 8), Conventional-Rinsed (n = 7), and -Enriched (n = 9)]. Fifty milliliters of each sample were subjected to DNA extraction followed by 16S rRNA sequencing. Proteobacteria and Firmicutes predominated the microbiota of both conventional and organic chickens, followed by low abundances of Bacteroidetes and Fusobacterium. While the abundance of Proteobacteria and Firmicutes remained unchanged in organic chicken irrespective of the methods used, a noticeable shift in the Proteobacteria and Firmicutes ratio (59%:39% in rinsed to 38%:60% in enriched) was observed in conventional chicken. Furthermore, the choice of method did not yield any differences in Abundance-Based Coverage Estimator, and Jackknife, among conventional and organic chickens but resulted in a statistically significant difference in the Shannon, Simpson, Chao1, and phylogenetic diversity indices (p < 0.05). The relative abundance of Salmonella and Campylobacter was less than 0.1%. The results suggested the WCE method provides a broad range of information on the chicken microbiome.

@article{
 title = {Cholera resurgence potentially induced by the consequences of climate in the El Niño phenomenon: an urgent call for strengthened cholera elimination in Africa},
 type = {article},
 year = {2023},
 keywords = {Africa,El Niño,Vibrio cholerae,cholera,cholera control,cholera elimination,climate},
 volume = {46},
 month = {9},
 publisher = {African Field Epidemiology Network},
 day = {1},
 id = {da640c41-0843-3aca-b8a7-e03ae1a00501},
 created = {2025-10-30T12:26:00.923Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.923Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {A resurgence in cholera cases has been observed throughout Africa during the first half of 2023. Among the many factors that drive cholera transmission, the ongoing climate phenomenon El Niño is likely to continue until March to May 2024. To prevent further cholera spread, it is critical to strengthen cholera control efforts in Africa.},
 bibtype = {article},
 author = {Makuntima, Nadège Taty and Bompangue, Didier and Moore, Sandra and de Richemond, Nancy Meschinet and Vandevelde, Thierry and Mwamba, Dieudonné and Colwell, Rita and Muyembe, Jean Jacques},
 doi = {10.11604/pamj.2023.46.96.42258},
 journal = {Pan African Medical Journal}
}

A resurgence in cholera cases has been observed throughout Africa during the first half of 2023. Among the many factors that drive cholera transmission, the ongoing climate phenomenon El Niño is likely to continue until March to May 2024. To prevent further cholera spread, it is critical to strengthen cholera control efforts in Africa.

@article{
 title = {Potential reservoirs of antimicrobial resistance in livestock waste and treated wastewater that can be disseminated to agricultural land},
 type = {article},
 year = {2023},
 keywords = {Antibiotic resistance genes,Antibiotic-resistant bacteria,Dairy lagoon,Manure,Virulence factor genes,Wastewater},
 volume = {872},
 month = {5},
 publisher = {Elsevier B.V.},
 day = {10},
 id = {fa0615e0-7bcb-3a53-a1da-3410c59777b9},
 created = {2025-10-30T12:26:01.108Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.108Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Livestock manure, dairy lagoon effluent, and treated wastewater are known reservoirs of antibiotic resistance genes (ARGs), antibiotic-resistant bacteria (ARB), and virulence factor genes (VFGs), and their application to agricultural farmland could be a serious public health threat. However, their dissemination to agricultural lands and impact on important geochemical pathways such as the nitrogen (N) cycle have not been jointly explored. In this study, shotgun metagenomic sequencing and analyses were performed to examine the diversity and composition of microbial communities, ARGs, VFGs, and N cycling genes in different livestock manure/lagoon and treated wastewater collected from concentrated animal feeding operations (CAFOs) and a municipal wastewater treatment plant along the west coast of the United States. Multivariate analysis showed that diversity indices of bacterial taxa from the different microbiomes were not significantly different based on InvSimpson (P = 0.05), but differences in ARG mechanisms were observed between swine manure and other microbiome sources. Comparative resistome profiling showed that ARGs in microbiome samples belonged to four core resistance classes: aminoglycosides (40–55 %), tetracyclines (30–45 %), beta-lactam-resistance (20–35 %), macrolides (18–30 %), and >50 % of the VFGs that the 24 microbiomes harbored were phyletically affiliated with two bacteria, Bacteroidetes fragilis and Enterobacter aerogenes. Network analysis based on Spearman correlation showed co-occurrence patterns between several genes such as transporter-gene and regulator, efflux pump and involved-in-polymyxin- resistance, aminoglycoside, beta-lactam, and macrolide with VFGs and bacterial taxa such as Firmicutes, Candidatus Themoplasmatota, Actinobacteria, and Bacteroidetes. Metabolic reconstruction of metagenome-assembled genome (MAGs) analysis showed that the most prevalent drug resistance mechanisms were associated with carbapenem resistance, multidrug resistance (MDR), and efflux pump. Bacteroidales was the main taxa involved in dissimilatory nitrate reduction (DNRA) in dairy lagoon effluent. This study demonstrates that the dissemination of waste from these sources can increase the spread of ARGs, ARB, and VFGs into agricultural lands, negatively impacting both soil and human health.},
 bibtype = {article},
 author = {Ibekwe, Abasiofiok M. and Bhattacharjee, Ananda S. and Phan, Duc and Ashworth, Daniel and Schmidt, Michael P. and Murinda, Shelton E. and Obayiuwana, Amarachukwu and Murry, Marcia A. and Schwartz, Gregory and Lundquist, Tryg and Ma, Jincai and Karathia, H. and Fanelli, B. and Hasan, Nur A. and Yang, Ching Hong},
 doi = {10.1016/j.scitotenv.2023.162194},
 journal = {Science of the Total Environment}
}

Livestock manure, dairy lagoon effluent, and treated wastewater are known reservoirs of antibiotic resistance genes (ARGs), antibiotic-resistant bacteria (ARB), and virulence factor genes (VFGs), and their application to agricultural farmland could be a serious public health threat. However, their dissemination to agricultural lands and impact on important geochemical pathways such as the nitrogen (N) cycle have not been jointly explored. In this study, shotgun metagenomic sequencing and analyses were performed to examine the diversity and composition of microbial communities, ARGs, VFGs, and N cycling genes in different livestock manure/lagoon and treated wastewater collected from concentrated animal feeding operations (CAFOs) and a municipal wastewater treatment plant along the west coast of the United States. Multivariate analysis showed that diversity indices of bacterial taxa from the different microbiomes were not significantly different based on InvSimpson (P = 0.05), but differences in ARG mechanisms were observed between swine manure and other microbiome sources. Comparative resistome profiling showed that ARGs in microbiome samples belonged to four core resistance classes: aminoglycosides (40–55 %), tetracyclines (30–45 %), beta-lactam-resistance (20–35 %), macrolides (18–30 %), and >50 % of the VFGs that the 24 microbiomes harbored were phyletically affiliated with two bacteria, Bacteroidetes fragilis and Enterobacter aerogenes. Network analysis based on Spearman correlation showed co-occurrence patterns between several genes such as transporter-gene and regulator, efflux pump and involved-in-polymyxin- resistance, aminoglycoside, beta-lactam, and macrolide with VFGs and bacterial taxa such as Firmicutes, Candidatus Themoplasmatota, Actinobacteria, and Bacteroidetes. Metabolic reconstruction of metagenome-assembled genome (MAGs) analysis showed that the most prevalent drug resistance mechanisms were associated with carbapenem resistance, multidrug resistance (MDR), and efflux pump. Bacteroidales was the main taxa involved in dissimilatory nitrate reduction (DNRA) in dairy lagoon effluent. This study demonstrates that the dissemination of waste from these sources can increase the spread of ARGs, ARB, and VFGs into agricultural lands, negatively impacting both soil and human health.

@article{
 title = {Analysis of Adeno-Associated Virus Serotype 8 (AAV8)-antibody complexes using epitope mapping by molecular imprinting leads to the identification of Fab peptides that potentially evade AAV8 neutralisation},
 type = {article},
 year = {2023},
 keywords = {Adeno-Associated Virus Serotype 8 (AAV8),Anti-AAV neutralising antibodies,Mass-spectrometric sequence analysis,Molecular imprinting,Peptide sequencing},
 volume = {52},
 month = {8},
 publisher = {Elsevier Inc.},
 day = {1},
 id = {5a95125c-62ff-378c-b879-c2e02275e069},
 created = {2025-10-30T12:28:33.536Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:36.013Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Gene therapy is a promising approach for treating genetic disorders by delivering therapeutic genes to replace or correct malfunctioning genes. However, the introduced gene therapy vector can trigger an immune response, leading to reduced efficacy and potential harm to the patient. To improve the efficiency and safety of gene therapy, preventing the immune response to the vector is crucial. This can be achieved through the use of immunosuppressive drugs, vector engineering to evade the immune system, or delivery methods that bypass the immune system altogether. By reducing the immune response, gene therapy can deliver therapeutic genes more effectively and potentially cure genetic diseases. In this study, a novel molecular imprinting technique, combined with mass-spectrometry and bioinformatics, was used to identify four antigen-binding fragments (Fab) sequences of Adeno-Associated Virus (AAV) - neutralising antibodies capable of binding to AAV. The identified Fab peptides were shown to prevent AAV8's binding to antibodies, demonstrating their potential to improve gene therapy efficiency by preventing the immune response.},
 bibtype = {article},
 author = {Piletska, Elena and Veron, Philippe and Bertin, Bérangère and Mingozzi, Federico and Jones, Donald and Norman, Rachel L. and Earley, Joseph and Karim, Kal and Garcia-Cruz, Alvaro and Piletsky, Sergey},
 doi = {10.1016/j.nano.2023.102691},
 journal = {Nanomedicine: Nanotechnology, Biology, and Medicine}
}

Gene therapy is a promising approach for treating genetic disorders by delivering therapeutic genes to replace or correct malfunctioning genes. However, the introduced gene therapy vector can trigger an immune response, leading to reduced efficacy and potential harm to the patient. To improve the efficiency and safety of gene therapy, preventing the immune response to the vector is crucial. This can be achieved through the use of immunosuppressive drugs, vector engineering to evade the immune system, or delivery methods that bypass the immune system altogether. By reducing the immune response, gene therapy can deliver therapeutic genes more effectively and potentially cure genetic diseases. In this study, a novel molecular imprinting technique, combined with mass-spectrometry and bioinformatics, was used to identify four antigen-binding fragments (Fab) sequences of Adeno-Associated Virus (AAV) - neutralising antibodies capable of binding to AAV. The identified Fab peptides were shown to prevent AAV8's binding to antibodies, demonstrating their potential to improve gene therapy efficiency by preventing the immune response.

@article{
 title = {Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use},
 type = {article},
 year = {2023},
 keywords = {high performance liquid chromatography,laboratory methods & tools,mass spectrometry,proteins},
 pages = {302-310},
 volume = {61},
 month = {1},
 publisher = {De Gruyter Open Ltd},
 day = {1},
 id = {2c9fa11b-0286-3684-848e-6a6849404e8c},
 created = {2025-10-30T12:28:33.561Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:37.220Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Objectives: During 2020, the UK’s Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity. Methods: Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/ MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study. Results: Analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7–39.1) demonstrated diagnostic sensitivity of 92.4% (87.4–95.5), specificity of 97.4% (94.0–98.9) and near total concordance with RT-qPCR (Cohen’s Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1–99.3), specificity 97.4% (94.0–98.9) and Cohen’s Kappa 0.95. Conclusions: This unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory.},
 bibtype = {article},
 author = {Hällqvist, Jenny and Lane, Dan and Shapanis, Andrew and Davis, Kayleigh and Heywood, Wendy E. and Doykov, Ivan and Śpiewak, Justyna and Ghansah, Nana and Keevil, Brian and Gupta, Pankaj and Jukes-Jones, Rebekah and Singh, Raj and Foley, Dominic and Vissers, Johannes P.C. and Pattison, Rebecca and Ferries, Samantha and Wardle, Robert and Bartlett, Amy and Calton, Lisa J. and Anderson, Leigh and Razavi, Morteza and Pearson, Terry and Pope, Matt and Yip, Richard and Ng, Leong L. and Nicholas, Benjamin I. and Bailey, Alistair and Noel, Dan and Dalton, R. Neil and Heales, Simon and Hopley, Christopher and Pitt, Andrew R. and Barran, Perdita and Jones, Donald J.L. and Mills, Kevin and Skipp, Paul and Carling, Rachel S.},
 doi = {10.1515/cclm-2022-1000},
 journal = {Clinical Chemistry and Laboratory Medicine},
 number = {2}
}

Objectives: During 2020, the UK’s Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity. Methods: Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/ MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study. Results: Analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7–39.1) demonstrated diagnostic sensitivity of 92.4% (87.4–95.5), specificity of 97.4% (94.0–98.9) and near total concordance with RT-qPCR (Cohen’s Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1–99.3), specificity 97.4% (94.0–98.9) and Cohen’s Kappa 0.95. Conclusions: This unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory.

@article{
 title = {NAD+ regulates nucleotide metabolism and genomic DNA replication},
 type = {article},
 year = {2023},
 pages = {1774-1786},
 volume = {25},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {019e0b02-3f11-310f-97c8-c08a95aec1c4},
 created = {2025-10-30T12:28:34.275Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:34.275Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The intricate orchestration of enzymatic activities involving nicotinamide adenine dinucleotide (NAD+) is essential for maintaining metabolic homeostasis and preserving genomic integrity. As a co-enzyme, NAD+ plays a key role in regulating metabolic pathways, such as glycolysis and Kreb’s cycle. ADP-ribosyltransferases (PARPs) and sirtuins rely on NAD+ to mediate post-translational modifications of target proteins. The activation of PARP1 in response to DNA breaks leads to rapid depletion of cellular NAD+ compromising cell viability. Therefore, the levels of NAD+ must be tightly regulated. Here we show that exogenous NAD+, but not its precursors, has a direct effect on mitochondrial activity. Short-term incubation with NAD+ boosts Kreb’s cycle and the electron transport chain and enhances pyrimidine biosynthesis. Extended incubation with NAD+ results in depletion of pyrimidines, accumulation of purines, activation of the replication stress response and cell cycle arrest. Moreover, a combination of NAD+ and 5-fluorouridine selectively kills cancer cells that rely on de novo pyrimidine synthesis. We propose an integrated model of how NAD+ regulates nucleotide metabolism, with relevance to healthspan, ageing and cancer therapy.},
 bibtype = {article},
 author = {Munk, Sebastian Howen Nesgaard and Merchut-Maya, Joanna Maria and Adelantado Rubio, Alba and Hall, Arnaldur and Pappas, George and Milletti, Giacomo and Lee, Myung Hee and Johnsen, Lea Giørtz and Guldberg, Per and Bartek, Jiri and Maya-Mendoza, Apolinar},
 doi = {10.1038/s41556-023-01280-z},
 journal = {Nature Cell Biology},
 number = {12}
}

The intricate orchestration of enzymatic activities involving nicotinamide adenine dinucleotide (NAD+) is essential for maintaining metabolic homeostasis and preserving genomic integrity. As a co-enzyme, NAD+ plays a key role in regulating metabolic pathways, such as glycolysis and Kreb’s cycle. ADP-ribosyltransferases (PARPs) and sirtuins rely on NAD+ to mediate post-translational modifications of target proteins. The activation of PARP1 in response to DNA breaks leads to rapid depletion of cellular NAD+ compromising cell viability. Therefore, the levels of NAD+ must be tightly regulated. Here we show that exogenous NAD+, but not its precursors, has a direct effect on mitochondrial activity. Short-term incubation with NAD+ boosts Kreb’s cycle and the electron transport chain and enhances pyrimidine biosynthesis. Extended incubation with NAD+ results in depletion of pyrimidines, accumulation of purines, activation of the replication stress response and cell cycle arrest. Moreover, a combination of NAD+ and 5-fluorouridine selectively kills cancer cells that rely on de novo pyrimidine synthesis. We propose an integrated model of how NAD+ regulates nucleotide metabolism, with relevance to healthspan, ageing and cancer therapy.

@article{
 title = {Increased circulating butyrate and ursodeoxycholate during probiotic intervention in humans with type 2 diabetes},
 type = {article},
 year = {2022},
 keywords = {semi-polar},
 pages = {1-18},
 volume = {22},
 websites = {https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-021-02415-8},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {39254efd-5e47-3f87-82f9-372835ca0128},
 created = {2025-07-07T13:25:37.073Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:20.948Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: An increasing body of evidence implicates the resident gut microbiota as playing a critical role in type 2 diabetes (T2D) pathogenesis. We previously reported significant improvement in postprandial glucose control in human participants with T2D following 12-week administration of a 5-strain novel probiotic formulation (‘WBF-011’) in a double-blind, randomized, placebo controlled setting (NCT03893422). While the clinical endpoints were encouraging, additional exploratory measurements were needed in order to link the motivating mechanistic hypothesis - increased short-chain fatty acids - with markers of disease. Results: Here we report targeted and untargeted metabolomic measurements on fasting plasma (n = 104) collected at baseline and end of intervention. Butyrate and ursodeoxycholate increased among participants randomized to WBF-011, along with compelling trends between butyrate and glycated haemoglobin (HbA1c). In vitro monoculture experiments demonstrated that the formulation’s C. butyricum strain efficiently synthesizes ursodeoxycholate from the primary bile acid chenodeoxycholate during butyrogenic growth. Untargeted metabolomics also revealed coordinated decreases in intermediates of fatty acid oxidation and bilirubin, potential secondary signatures for metabolic improvement. Finally, improvement in HbA1c was limited almost entirely to participants not using sulfonylurea drugs. We show that these drugs can inhibit growth of formulation strains in vitro. Conclusion: To our knowledge, this is the first description of an increase in circulating butyrate or ursodeoxycholate following a probiotic intervention in humans with T2D, adding support for the possibility of a targeted microbiome-based approach to assist in the management of T2D. The efficient synthesis of UDCA by C. butyricum is also likely of interest to investigators of its use as a probiotic in other disease settings. The potential for inhibitory interaction between sulfonylurea drugs and gut microbiota should be considered carefully in the design of future studies.},
 bibtype = {article},
 author = {McMurdie, Paul J. and Stoeva, Magdalena K. and Justice, Nicholas and Nemchek, Madeleine and Sieber, Christian M.K. and Tyagi, Surabhi and Gines, Jessica and Skennerton, Connor T. and Souza, Michael and Kolterman, Orville and Eid, John},
 doi = {10.1186/S12866-021-02415-8/FIGURES/5},
 journal = {BMC Microbiology},
 number = {1}
}

Background: An increasing body of evidence implicates the resident gut microbiota as playing a critical role in type 2 diabetes (T2D) pathogenesis. We previously reported significant improvement in postprandial glucose control in human participants with T2D following 12-week administration of a 5-strain novel probiotic formulation (‘WBF-011’) in a double-blind, randomized, placebo controlled setting (NCT03893422). While the clinical endpoints were encouraging, additional exploratory measurements were needed in order to link the motivating mechanistic hypothesis - increased short-chain fatty acids - with markers of disease. Results: Here we report targeted and untargeted metabolomic measurements on fasting plasma (n = 104) collected at baseline and end of intervention. Butyrate and ursodeoxycholate increased among participants randomized to WBF-011, along with compelling trends between butyrate and glycated haemoglobin (HbA1c). In vitro monoculture experiments demonstrated that the formulation’s C. butyricum strain efficiently synthesizes ursodeoxycholate from the primary bile acid chenodeoxycholate during butyrogenic growth. Untargeted metabolomics also revealed coordinated decreases in intermediates of fatty acid oxidation and bilirubin, potential secondary signatures for metabolic improvement. Finally, improvement in HbA1c was limited almost entirely to participants not using sulfonylurea drugs. We show that these drugs can inhibit growth of formulation strains in vitro. Conclusion: To our knowledge, this is the first description of an increase in circulating butyrate or ursodeoxycholate following a probiotic intervention in humans with T2D, adding support for the possibility of a targeted microbiome-based approach to assist in the management of T2D. The efficient synthesis of UDCA by C. butyricum is also likely of interest to investigators of its use as a probiotic in other disease settings. The potential for inhibitory interaction between sulfonylurea drugs and gut microbiota should be considered carefully in the design of future studies.

@article{
 title = {Human milk oligosaccharide-sharing by a consortium of infant derived Bifidobacterium species},
 type = {article},
 year = {2022},
 keywords = {MCF,Spent media},
 pages = {1-14},
 volume = {12},
 websites = {https://www.nature.com/articles/s41598-022-07904-y},
 month = {3},
 publisher = {Nature Publishing Group},
 day = {9},
 id = {f3a15f54-ed0b-3300-8208-b3f27f9ae90f},
 created = {2025-07-07T13:25:37.393Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:21.288Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Bifidobacteria are associated with a host of health benefits and are typically dominant in the gut microbiota of healthy, breast-fed infants. A key adaptation, facilitating the establishment of these species, is their ability to consume particular sugars, known as human milk oligosaccharides (HMO), which are abundantly found in breastmilk. In the current study, we aimed to characterise the co-operative metabolism of four commercial infant-derived bifidobacteria (Bifidobacterium bifidum R0071, Bifidobacterium breve M-16V, Bifidobacterium infantis R0033, and Bifidobacterium infantis M-63) when grown on HMO. Three different HMO substrates (2′-fucosyllactose alone and oligosaccharides isolated from human milk representing non-secretor and secretor status) were employed. The four-strain combination resulted in increased bifidobacterial numbers (> 21%) in comparison to single strain cultivation. The relative abundance of B. breve increased by > 30% during co-cultivation with the other strains despite demonstrating limited ability to assimilate HMO in mono-culture. HPLC analysis revealed strain-level variations in HMO consumption. Metabolomics confirmed the production of formate, acetate, 1,2-propanediol, and lactate with an overall increase in such metabolites during co-cultivation. These results support the concept of positive co-operation between multiple bifidobacterial strains during HMO utilisation which may result in higher cell numbers and a potentially healthier balance of metabolites.},
 bibtype = {article},
 author = {Walsh, Clodagh and Lane, Jonathan A. and van Sinderen, Douwe and Hickey, Rita M.},
 doi = {10.1038/s41598-022-07904-y},
 journal = {Scientific Reports 2022 12:1},
 number = {1}
}

Bifidobacteria are associated with a host of health benefits and are typically dominant in the gut microbiota of healthy, breast-fed infants. A key adaptation, facilitating the establishment of these species, is their ability to consume particular sugars, known as human milk oligosaccharides (HMO), which are abundantly found in breastmilk. In the current study, we aimed to characterise the co-operative metabolism of four commercial infant-derived bifidobacteria (Bifidobacterium bifidum R0071, Bifidobacterium breve M-16V, Bifidobacterium infantis R0033, and Bifidobacterium infantis M-63) when grown on HMO. Three different HMO substrates (2′-fucosyllactose alone and oligosaccharides isolated from human milk representing non-secretor and secretor status) were employed. The four-strain combination resulted in increased bifidobacterial numbers (> 21%) in comparison to single strain cultivation. The relative abundance of B. breve increased by > 30% during co-cultivation with the other strains despite demonstrating limited ability to assimilate HMO in mono-culture. HPLC analysis revealed strain-level variations in HMO consumption. Metabolomics confirmed the production of formate, acetate, 1,2-propanediol, and lactate with an overall increase in such metabolites during co-cultivation. These results support the concept of positive co-operation between multiple bifidobacterial strains during HMO utilisation which may result in higher cell numbers and a potentially healthier balance of metabolites.

@article{
 title = {CmP Signaling Network Leads to Identification of Prognostic Biomarkers for Triple-Negative Breast Cancer in Caucasian Women},
 type = {article},
 year = {2022},
 keywords = {Biomarkers,Carcinogenesis,Female,Humans,Johnathan Abou-Fadel,Jun Zhang,MEDLINE,Muaz Bhalli,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Prognosis,Proteomics,PubMed Abstract,Triple Negative Breast Neoplasms* / genetics,Triple Negative Breast Neoplasms* / metabolism,doi:10.1089/gtmb.2021.0221,pmid:35481969},
 pages = {198-219},
 volume = {26},
 websites = {https://pubmed.ncbi.nlm.nih.gov/35481969/},
 month = {4},
 publisher = {Genet Test Mol Biomarkers},
 day = {1},
 id = {cd32ccab-19f2-3ca6-b6b5-3d64e487d30b},
 created = {2025-07-07T13:25:37.799Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:37.799Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Objective: Triple-negative breast cancer (TNBC) constitutes ∼15% of all diagnosed invasive breast cancer cases with limited options for treatment since immunotherapies that target ER, PR, and HER2 receptors are ineffective. Progesterone (PRG) can induce its effects through either classic, nonclassic, or combined responses by binding to classic nuclear PRG receptors (nPRs) or nonclassic membrane PRG receptors (mPRs). Under PRG-induced actions, we previously demonstrated that the CCM signaling complex (CSC) can couple both nPRs and mPRs into a CmPn signaling network, which plays an important role during nPR(+) breast cancer tumorigenesis. We recently defined the novel CmP signaling network in African American women (AAW)-derived TNBC cells, which overlapped with our previously defined CmPn network in nPR(+) breast cancer cells. Methods: Under mPR-specific steroid actions, we measured alterations to key tumorigenic pathways in Caucasian American women (CAW)- derived TNBC cells, with RNAseq/proteomic and systems biology approaches. Exemption from ethics approval from IRB: This study only utilized cultured NBC cell lines with publicly available TNBC clinical data sets. Results: Our results demonstrated that TNBCs in CAW share similar altered signaling pathways, as TNBCs in AAW, under mPR-specific steroid actions, demonstrating the overall aggressive nature of TNBCs, regardless of racial differences. Furthermore, in this report, we have deconvoluted the CmP signalosome, using systems biology approaches and CAW-TNBC clinical data, to identify 21 new CAW-TNBC-specific prognostic biomarkers that reinforce the definitive role of CSC and mPR signaling during CAW-TNBC tumorigenesis. Conclusion: This new set of potential prognostic biomarkers may revolutionize molecular mechanisms and currently known concepts of tumorigenesis in CAW-TNBCs, leading to hopeful new therapeutic strategies.},
 bibtype = {article},
 author = {Abou-Fadel, Johnathan and Bhalli, Muaz and Grajeda, Brian and Zhang, Jun},
 doi = {10.1089/GTMB.2021.0221},
 journal = {Genetic testing and molecular biomarkers},
 number = {4}
}

Objective: Triple-negative breast cancer (TNBC) constitutes ∼15% of all diagnosed invasive breast cancer cases with limited options for treatment since immunotherapies that target ER, PR, and HER2 receptors are ineffective. Progesterone (PRG) can induce its effects through either classic, nonclassic, or combined responses by binding to classic nuclear PRG receptors (nPRs) or nonclassic membrane PRG receptors (mPRs). Under PRG-induced actions, we previously demonstrated that the CCM signaling complex (CSC) can couple both nPRs and mPRs into a CmPn signaling network, which plays an important role during nPR(+) breast cancer tumorigenesis. We recently defined the novel CmP signaling network in African American women (AAW)-derived TNBC cells, which overlapped with our previously defined CmPn network in nPR(+) breast cancer cells. Methods: Under mPR-specific steroid actions, we measured alterations to key tumorigenic pathways in Caucasian American women (CAW)- derived TNBC cells, with RNAseq/proteomic and systems biology approaches. Exemption from ethics approval from IRB: This study only utilized cultured NBC cell lines with publicly available TNBC clinical data sets. Results: Our results demonstrated that TNBCs in CAW share similar altered signaling pathways, as TNBCs in AAW, under mPR-specific steroid actions, demonstrating the overall aggressive nature of TNBCs, regardless of racial differences. Furthermore, in this report, we have deconvoluted the CmP signalosome, using systems biology approaches and CAW-TNBC clinical data, to identify 21 new CAW-TNBC-specific prognostic biomarkers that reinforce the definitive role of CSC and mPR signaling during CAW-TNBC tumorigenesis. Conclusion: This new set of potential prognostic biomarkers may revolutionize molecular mechanisms and currently known concepts of tumorigenesis in CAW-TNBCs, leading to hopeful new therapeutic strategies.

@article{
 title = {Human milk oligosaccharides induce acute yet reversible compositional changes in the gut microbiota of conventional mice linked to a reduction of butyrate levels},
 type = {article},
 year = {2022},
 keywords = {Andrea Qvortrup Holst,Harshitha Jois,MEDLINE,Martin Iain Bahl,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,PMC10117735,PubMed Abstract,doi:10.1093/femsml/uqac006,pmid:37223362},
 volume = {3},
 websites = {https://pubmed.ncbi.nlm.nih.gov/37223362/},
 month = {6},
 publisher = {Microlife},
 day = {22},
 id = {fc01237f-1922-3157-968d-bf54e391e768},
 created = {2025-07-07T13:25:38.163Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:21.794Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Human Milk Oligosaccharides (HMOs) are glycans with prebiotic properties known to drive microbial selection in the infant gut, which in turn influences immune development and future health. Bifidobacteria are specialized in HMO degradation and frequently dominate the gut microbiota of breastfed infants. However, some species of Bacteroidaceae also degrade HMOs, which may prompt selection also of these species in the gut microbiota. To investigate to what extent specific HMOs affect the abundance of naturally occurring Bacteroidaceae species in a complex mammalian gut environment, we conducted a study in 40 female NMRI mice administered three structurally different HMOs, namely 6’sialyllactose (6'SL, n = 8), 3-fucosyllactose (3FL, n = 16), and Lacto-N-Tetraose (LNT, n = 8), through drinking water (5%). Compared to a control group receiving unsupplemented drinking water (n = 8), supplementation with each of the HMOs significantly increased both the absolute and relative abundance of Bacteroidaceae species in faecal samples and affected the overall microbial composition analyzed by 16s rRNA amplicon sequencing. The compositional differences were mainly attributed to an increase in the relative abundance of the genus Phocaeicola (formerly Bacteroides) and a concomitant decrease of the genus Lacrimispora (formerly Clostridium XIVa cluster). During a 1-week washout period performed specifically for the 3FL group, this effect was reversed. Short-chain fatty acid analysis of faecal water revealed a decrease in acetate, butyrate and isobutyrate levels in animals supplemented with 3FL, which may reflect the observed decrease in the Lacrimispora genus. This study highlights HMO-driven Bacteroidaceae selection in the gut environment, which may cause a reduction of butyrate-producing clostridia.},
 bibtype = {article},
 author = {Holst, Andrea Qvortrup and Jois, Harshitha and Laursen, Martin Frederik and Sommer, Morten O A and Licht, Tine Rask and Bahl, Martin Iain},
 doi = {10.1093/FEMSML/UQAC006},
 journal = {microLife}
}

Human Milk Oligosaccharides (HMOs) are glycans with prebiotic properties known to drive microbial selection in the infant gut, which in turn influences immune development and future health. Bifidobacteria are specialized in HMO degradation and frequently dominate the gut microbiota of breastfed infants. However, some species of Bacteroidaceae also degrade HMOs, which may prompt selection also of these species in the gut microbiota. To investigate to what extent specific HMOs affect the abundance of naturally occurring Bacteroidaceae species in a complex mammalian gut environment, we conducted a study in 40 female NMRI mice administered three structurally different HMOs, namely 6’sialyllactose (6'SL, n = 8), 3-fucosyllactose (3FL, n = 16), and Lacto-N-Tetraose (LNT, n = 8), through drinking water (5%). Compared to a control group receiving unsupplemented drinking water (n = 8), supplementation with each of the HMOs significantly increased both the absolute and relative abundance of Bacteroidaceae species in faecal samples and affected the overall microbial composition analyzed by 16s rRNA amplicon sequencing. The compositional differences were mainly attributed to an increase in the relative abundance of the genus Phocaeicola (formerly Bacteroides) and a concomitant decrease of the genus Lacrimispora (formerly Clostridium XIVa cluster). During a 1-week washout period performed specifically for the 3FL group, this effect was reversed. Short-chain fatty acid analysis of faecal water revealed a decrease in acetate, butyrate and isobutyrate levels in animals supplemented with 3FL, which may reflect the observed decrease in the Lacrimispora genus. This study highlights HMO-driven Bacteroidaceae selection in the gut environment, which may cause a reduction of butyrate-producing clostridia.

@article{
 title = {Metabolic systems analysis identifies a novel mechanism contributing to shock in patients with endotheliopathy of trauma (EoT) involving thromboxane A2 and LTC4},
 type = {article},
 year = {2022},
 keywords = {MCF,RP,semi-polar},
 volume = {15},
 websites = {https://pubmed.ncbi.nlm.nih.gov/35813244/},
 month = {8},
 publisher = {Matrix Biol Plus},
 day = {1},
 id = {c8c5c4ca-1d5d-3a93-8611-56d6545eb259},
 created = {2025-07-07T13:25:38.571Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:22.156Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Purpose: Endotheliopathy of trauma (EoT), as defined by circulating levels of syndecan-1 ≥ 40 ng/mL, has been reported to be associated with significantly increased transfusion requirements and a doubled 30-day mortality. Increased shedding of the glycocalyx points toward the endothelial cell membrane composition as important for the clinical outcome being the rationale for this study. Results: The plasma metabolome of 95 severely injured trauma patients was investigated by mass spectrometry, and patients with EoT vs. non-EoT were compared by partial least square-discriminant analysis, identifying succinic acid as the top metabolite to differentiate EoT and non-EoT patients (VIP score = 3). EoT and non-EoT patients’ metabolic flux profile was inferred by integrating the corresponding plasma metabolome data into a genome-scale metabolic network reconstruction analysis and performing a functional study of the metabolic capabilities of each group. Model predictions showed a decrease in cholesterol metabolism secondary to impaired mevalonate synthesis in EoT compared to non-EoT patients. Intracellular task analysis indicated decreased synthesis of thromboxanA2 and leukotrienes, as well as a lower carnitine palmitoyltransferase I activity in EoT compared to non-EoT patients. Sensitivity analysis also showed a significantly high dependence of eicosanoid-associated metabolic tasks on alpha-linolenic acid as unique to EoT patients. Conclusions: Model-driven analysis of the endothelial cells’ metabolism identified potential novel targets as impaired thromboxane A2 and leukotriene synthesis in EoT patients when compared to non-EoT patients. Reduced thromboxane A2 and leukotriene availability in the microvasculature impairs vasoconstriction ability and may thus contribute to shock in EoT patients. These findings are supported by extensive scientific literature; however, further investigations are required on these findings.},
 bibtype = {article},
 author = {Henriksen, Hanne H. and Marín de Mas, Igor and Herand, Helena and Krocker, Joseph and Wade, Charles E. and Johansson, Pär I.},
 doi = {10.1016/J.MBPLUS.2022.100115},
 journal = {Matrix biology plus}
}

Purpose: Endotheliopathy of trauma (EoT), as defined by circulating levels of syndecan-1 ≥ 40 ng/mL, has been reported to be associated with significantly increased transfusion requirements and a doubled 30-day mortality. Increased shedding of the glycocalyx points toward the endothelial cell membrane composition as important for the clinical outcome being the rationale for this study. Results: The plasma metabolome of 95 severely injured trauma patients was investigated by mass spectrometry, and patients with EoT vs. non-EoT were compared by partial least square-discriminant analysis, identifying succinic acid as the top metabolite to differentiate EoT and non-EoT patients (VIP score = 3). EoT and non-EoT patients’ metabolic flux profile was inferred by integrating the corresponding plasma metabolome data into a genome-scale metabolic network reconstruction analysis and performing a functional study of the metabolic capabilities of each group. Model predictions showed a decrease in cholesterol metabolism secondary to impaired mevalonate synthesis in EoT compared to non-EoT patients. Intracellular task analysis indicated decreased synthesis of thromboxanA2 and leukotrienes, as well as a lower carnitine palmitoyltransferase I activity in EoT compared to non-EoT patients. Sensitivity analysis also showed a significantly high dependence of eicosanoid-associated metabolic tasks on alpha-linolenic acid as unique to EoT patients. Conclusions: Model-driven analysis of the endothelial cells’ metabolism identified potential novel targets as impaired thromboxane A2 and leukotriene synthesis in EoT patients when compared to non-EoT patients. Reduced thromboxane A2 and leukotriene availability in the microvasculature impairs vasoconstriction ability and may thus contribute to shock in EoT patients. These findings are supported by extensive scientific literature; however, further investigations are required on these findings.

@article{
 title = {Targeted plasma metabolomics in resuscitated comatose out-of-hospital cardiac arrest patients},
 type = {article},
 year = {2022},
 keywords = {MCF,semi-polar},
 pages = {163-171},
 volume = {179},
 websites = {https://pubmed.ncbi.nlm.nih.gov/35753507/},
 month = {10},
 publisher = {Resuscitation},
 day = {1},
 id = {500ca218-e6e0-31ff-8705-3676884fe4d6},
 created = {2025-07-07T13:25:38.920Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:22.535Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death. Even if successfully resuscitated, mortality remains high due to ischemic and reperfusion injury (I/R). The oxygen deprivation leads to a metabolic derangement amplified upon reperfusion resulting in an uncontrolled generation of reactive oxygen species in the mitochondria triggering cell death mechanisms. The understanding of I/R injury in humans following OHCA remains sparse, with no existing treatment to attenuate the reperfusion injury. Aim: To describe metabolic derangement in patients following resuscitated OHCA. Methods: Plasma from consecutive resuscitated unconscious OHCA patients drawn at hospital admission were analyzed using ultra-performance-liquid-mass-spectrometry. Sixty-one metabolites were prespecified for quantification and studied. Results: In total, 163 patients were included, of which 143 (88%) were men, and the median age was 62 years (53–68). All measured metabolites from the tricarboxylic acid (TCA) cycle were significantly higher in non-survivors vs. survivors (180-days survival). Hierarchical clustering identified four clusters (A-D) of patients with distinct metabolic profiles. Cluster A and B had higher levels of TCA metabolites, amino acids and acylcarnitine species compared to C and D. The mortality was significantly higher in cluster A and B (A:62% and B:59% vs. C:21 % and D:24%, p < 0.001). Cluster A and B had longer time to return of spontaneous circulation (A:33 min (21–43), B:27 min (24–35), C:18 min (13–28), and D:18 min (12–25), p < 0.001). Conclusion: Circulating levels of metabolites from the TCA cycle best described the variance between survivors and non-survivors. Four different metabolic phenotypes with significantly different mortality were identified.},
 bibtype = {article},
 author = {Paulin Beske, Rasmus and Henriksen, Hanne H. and Obling, Laust and Kjærgaard, Jesper and Bro-Jeppesen, John and Nielsen, Niklas and Johansson, Pär I. and Hassager, Christian},
 doi = {10.1016/J.RESUSCITATION.2022.06.010},
 journal = {Resuscitation}
}

Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death. Even if successfully resuscitated, mortality remains high due to ischemic and reperfusion injury (I/R). The oxygen deprivation leads to a metabolic derangement amplified upon reperfusion resulting in an uncontrolled generation of reactive oxygen species in the mitochondria triggering cell death mechanisms. The understanding of I/R injury in humans following OHCA remains sparse, with no existing treatment to attenuate the reperfusion injury. Aim: To describe metabolic derangement in patients following resuscitated OHCA. Methods: Plasma from consecutive resuscitated unconscious OHCA patients drawn at hospital admission were analyzed using ultra-performance-liquid-mass-spectrometry. Sixty-one metabolites were prespecified for quantification and studied. Results: In total, 163 patients were included, of which 143 (88%) were men, and the median age was 62 years (53–68). All measured metabolites from the tricarboxylic acid (TCA) cycle were significantly higher in non-survivors vs. survivors (180-days survival). Hierarchical clustering identified four clusters (A-D) of patients with distinct metabolic profiles. Cluster A and B had higher levels of TCA metabolites, amino acids and acylcarnitine species compared to C and D. The mortality was significantly higher in cluster A and B (A:62% and B:59% vs. C:21 % and D:24%, p < 0.001). Cluster A and B had longer time to return of spontaneous circulation (A:33 min (21–43), B:27 min (24–35), C:18 min (13–28), and D:18 min (12–25), p < 0.001). Conclusion: Circulating levels of metabolites from the TCA cycle best described the variance between survivors and non-survivors. Four different metabolic phenotypes with significantly different mortality were identified.

@article{
 title = {Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects},
 type = {article},
 year = {2022},
 keywords = {polar},
 volume = {40},
 websites = {https://pubmed.ncbi.nlm.nih.gov/36001966/},
 month = {8},
 publisher = {Cell Rep},
 day = {23},
 id = {ae6559f3-decf-3154-9a38-324eb150e02d},
 created = {2025-07-07T13:25:39.262Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:22.921Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Immunotherapy is improving the prognosis and survival of cancer patients, but despite encouraging outcomes in different cancers, the majority of tumors are resistant to it, and the immunotherapy combinations are often accompanied by severe side effects. Here, we show that a periodic fasting-mimicking diet (FMD) can act on the tumor microenvironment and increase the efficacy of immunotherapy (anti-PD-L1 and anti-OX40) against the poorly immunogenic triple-negative breast tumors (TNBCs) by expanding early exhausted effector T cells, switching the cancer metabolism from glycolytic to respiratory, and reducing collagen deposition. Furthermore, FMD reduces the occurrence of immune-related adverse events (irAEs) by preventing the hyperactivation of the immune response. These results indicate that FMD cycles have the potential to enhance the efficacy of anti-cancer immune responses, expand the portion of tumors sensitive to immunotherapy, and reduce its side effects.},
 bibtype = {article},
 author = {Cortellino, Salvatore and Raveane, Alessandro and Chiodoni, Claudia and Delfanti, Gloria and Pisati, Federica and Spagnolo, Vanessa and Visco, Euplio and Fragale, Giuseppe and Ferrante, Federica and Magni, Serena and Iannelli, Fabio and Zanardi, Federica and Casorati, Giulia and Bertolini, Francesco and Dellabona, Paolo and Colombo, Mario P. and Tripodo, Claudio and Longo, Valter D.},
 doi = {10.1016/J.CELREP.2022.111256},
 journal = {Cell reports},
 number = {8}
}

Immunotherapy is improving the prognosis and survival of cancer patients, but despite encouraging outcomes in different cancers, the majority of tumors are resistant to it, and the immunotherapy combinations are often accompanied by severe side effects. Here, we show that a periodic fasting-mimicking diet (FMD) can act on the tumor microenvironment and increase the efficacy of immunotherapy (anti-PD-L1 and anti-OX40) against the poorly immunogenic triple-negative breast tumors (TNBCs) by expanding early exhausted effector T cells, switching the cancer metabolism from glycolytic to respiratory, and reducing collagen deposition. Furthermore, FMD reduces the occurrence of immune-related adverse events (irAEs) by preventing the hyperactivation of the immune response. These results indicate that FMD cycles have the potential to enhance the efficacy of anti-cancer immune responses, expand the portion of tumors sensitive to immunotherapy, and reduce its side effects.

@article{
 title = {Dysregulated Sulfide Metabolism in Multiple Sclerosis: Serum and Vascular Endothelial Inflammatory Responses},
 type = {article},
 year = {2022},
 keywords = {semi-polar},
 pages = {570},
 volume = {29},
 websites = {/pmc/articles/PMC9502521/,/pmc/articles/PMC9502521/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502521/},
 month = {9},
 publisher = {Multidisciplinary Digital Publishing Institute  (MDPI)},
 day = {1},
 id = {93561bf9-1579-3f40-8b18-677381a92934},
 created = {2025-07-07T13:25:39.606Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:23.270Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Multiple sclerosis (MS) is a leading cause of neurodegenerative disability in younger individuals. When diagnosed early, MS can be managed more effectively, stabilizing clinical symptoms and delaying disease progression. The identification of specific serum biomarkers for early-stage MS could facilitate more successful treatment of this condition. Because MS is an inflammatory disease, we assessed changes in enzymes of the endothelial hydrogen sulfide (H2S) pathway in response to inflammatory cytokines. Blotting analysis was conducted to detect Cystathionine γ-lyase (CSE), Cystathionine beta synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST) in human brain microvascular endothelial apical and basolateral microparticles (MPs) and cells following exposure to tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). CSE was increased in MPs and cells by exposure to TNF-α/IFN-γ; CBS was elevated in apical MPs but not in cells or basolateral MPs; MST was not significantly affected by cytokine exposure. To test how our findings relate to MS patients, we evaluated levels of CSE, CBS, and MST in serum samples from healthy control and MS patients. We found significantly decreased levels of CBS and MST (p = 0.0004, 0.009) in MS serum samples, whereas serum levels of CSE were marginally increased (p = 0.06). These observations support increased CSE and lower CBS and MST expression being associated with the vascular inflammation in MS. These changes in endothelial-derived sulfide enzymes at sites of inflammation in the brain may help to explain sulfide-dependent changes in vascular dysfunction/neuroinflammation underlying MS. These findings further support the use of serum samples to assess enzymatic biomarkers derived from circulating MPs. For example, “liquid biopsy” can be an important tool for allowing early diagnosis of MS, prior to the advanced progression of neurodegeneration associated with this disease.},
 bibtype = {article},
 author = {Veerareddy, Pooja and Dao, Nhi and Yun, Jungmi W. and Stokes, Karen Y. and Disbrow, Elizabeth and Kevil, Christopher G. and Cvek, Urska and Trutschl, Marjan and Kilgore, Philip and Ramanathan, Murali and Zivadinov, Robert and Alexander, Jonathan S.},
 doi = {10.3390/PATHOPHYSIOLOGY29030044},
 journal = {Pathophysiology},
 number = {3}
}

Multiple sclerosis (MS) is a leading cause of neurodegenerative disability in younger individuals. When diagnosed early, MS can be managed more effectively, stabilizing clinical symptoms and delaying disease progression. The identification of specific serum biomarkers for early-stage MS could facilitate more successful treatment of this condition. Because MS is an inflammatory disease, we assessed changes in enzymes of the endothelial hydrogen sulfide (H2S) pathway in response to inflammatory cytokines. Blotting analysis was conducted to detect Cystathionine γ-lyase (CSE), Cystathionine beta synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST) in human brain microvascular endothelial apical and basolateral microparticles (MPs) and cells following exposure to tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). CSE was increased in MPs and cells by exposure to TNF-α/IFN-γ; CBS was elevated in apical MPs but not in cells or basolateral MPs; MST was not significantly affected by cytokine exposure. To test how our findings relate to MS patients, we evaluated levels of CSE, CBS, and MST in serum samples from healthy control and MS patients. We found significantly decreased levels of CBS and MST (p = 0.0004, 0.009) in MS serum samples, whereas serum levels of CSE were marginally increased (p = 0.06). These observations support increased CSE and lower CBS and MST expression being associated with the vascular inflammation in MS. These changes in endothelial-derived sulfide enzymes at sites of inflammation in the brain may help to explain sulfide-dependent changes in vascular dysfunction/neuroinflammation underlying MS. These findings further support the use of serum samples to assess enzymatic biomarkers derived from circulating MPs. For example, “liquid biopsy” can be an important tool for allowing early diagnosis of MS, prior to the advanced progression of neurodegeneration associated with this disease.

@article{
 title = {Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient: a case report},
 type = {article},
 year = {2022},
 keywords = {SCFA},
 pages = {1-14},
 volume = {10},
 websites = {https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01394-w},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {a02fa5ca-0b1d-3215-ae27-ac18a46e2f8a},
 created = {2025-07-07T13:25:39.949Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:23.711Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment. Methods: A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults. Results: The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient’s gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer. Conclusions: The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. [MediaObject not available: see fulltext.]},
 bibtype = {article},
 author = {Wei, Shaodong and Jespersen, Marie Louise and Baunwall, Simon Mark Dahl and Myers, Pernille Neve and Smith, Emilie Milton and Dahlerup, Jens Frederik and Rasmussen, Simon and Nielsen, Henrik Bjørn and Licht, Tine Rask and Bahl, Martin Iain and Hvas, Christian Lodberg},
 doi = {10.1186/S40168-022-01394-W/FIGURES/4},
 journal = {Microbiome},
 number = {1}
}

Background: Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment. Methods: A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults. Results: The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient’s gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer. Conclusions: The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. [MediaObject not available: see fulltext.]

@article{
 title = {The circulating plasma metabolome of Neoparamoeba perurans-infected Atlantic salmon (Salmo salar)},
 type = {article},
 year = {2022},
 keywords = {semi-polar},
 volume = {166},
 websites = {https://pubmed.ncbi.nlm.nih.gov/35472502/},
 month = {5},
 publisher = {Microb Pathog},
 day = {1},
 id = {c875ee5f-3657-3aab-84a5-a8bafefbb79f},
 created = {2025-07-07T13:25:40.302Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:24.075Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Metabolomics can provide insights into the dynamic small-molecule fluctuations occurring in response to infection and has become a valuable tool in studying the pathophysiology of diseases in recent years. However, its application in fish disease research is limited. Here, we report the circulating plasma metabolome of Atlantic salmon (Salmo salar) experimentally infected with Neoparamoeba perurans—the causative agent of amoebic gill disease (AGD). Plasma samples were collected from fish with varying degrees of infection inferred from an external gross morphological score of gill pathology (i.e., gill score [GS] 1 – GS3), where a higher GS indicates advanced infection stage. Uninfected fish (GS0) served as the control. Typical pathologies associated with AGD infection, such as hyperplastic lesions and lamellar fusion, were evident in infected gill samples. Plasma metabolites were identified by ultra-performance liquid chromatography coupled with a high-resolution quadrupole-orbitrap mass spectrometer. Identification of compounds were performed at four levels of certainty, where level 1 provided the most accurate compound identity. A total of 900 compounds were detected in the samples of which 143 were annotated at level 3, 68 on level 2b, 74 on level 2a, and 66 on level 1. Versus GS0, GS1 showed the highest number of significantly affected metabolites (104), which decreased with a higher GS. Adrenaline and adenosine were the two Level 1 compounds significantly affected by AGD regardless of GS, with the former increasing and the latter decreasing in infected fish. Hippuric acid significantly increased in GS1 and GS2, while the tryptophan metabolite indole-3-lactic acid decreased in response to the initial stage of infection but returned to basal levels at a higher GS. There were ten significantly affected metabolic pathways: Eight of which were significantly downregulated while two were downregulated in GS1 relative to GS0. The super-pathway of purine nucleotide salvage was enriched both within the upregulated metabolites in GS1vsGS0 and the down-regulated metabolites in GS3vsGS1. This is the first report on the circulating plasma metabolome of AGD infected salmon, and the results show that low infection levels resulted in a more dramatic metabolomic dysregulation than advanced infection stages. The metabolites identified are potential biological markers for the systemic physiological impact of AGD.},
 bibtype = {article},
 author = {Lazado, Carlo C. and Breiland, Mette W. and Furtado, Francisco and Burgerhout, Erik and Strand, David},
 doi = {10.1016/J.MICPATH.2022.105553},
 journal = {Microbial pathogenesis}
}

Metabolomics can provide insights into the dynamic small-molecule fluctuations occurring in response to infection and has become a valuable tool in studying the pathophysiology of diseases in recent years. However, its application in fish disease research is limited. Here, we report the circulating plasma metabolome of Atlantic salmon (Salmo salar) experimentally infected with Neoparamoeba perurans—the causative agent of amoebic gill disease (AGD). Plasma samples were collected from fish with varying degrees of infection inferred from an external gross morphological score of gill pathology (i.e., gill score [GS] 1 – GS3), where a higher GS indicates advanced infection stage. Uninfected fish (GS0) served as the control. Typical pathologies associated with AGD infection, such as hyperplastic lesions and lamellar fusion, were evident in infected gill samples. Plasma metabolites were identified by ultra-performance liquid chromatography coupled with a high-resolution quadrupole-orbitrap mass spectrometer. Identification of compounds were performed at four levels of certainty, where level 1 provided the most accurate compound identity. A total of 900 compounds were detected in the samples of which 143 were annotated at level 3, 68 on level 2b, 74 on level 2a, and 66 on level 1. Versus GS0, GS1 showed the highest number of significantly affected metabolites (104), which decreased with a higher GS. Adrenaline and adenosine were the two Level 1 compounds significantly affected by AGD regardless of GS, with the former increasing and the latter decreasing in infected fish. Hippuric acid significantly increased in GS1 and GS2, while the tryptophan metabolite indole-3-lactic acid decreased in response to the initial stage of infection but returned to basal levels at a higher GS. There were ten significantly affected metabolic pathways: Eight of which were significantly downregulated while two were downregulated in GS1 relative to GS0. The super-pathway of purine nucleotide salvage was enriched both within the upregulated metabolites in GS1vsGS0 and the down-regulated metabolites in GS3vsGS1. This is the first report on the circulating plasma metabolome of AGD infected salmon, and the results show that low infection levels resulted in a more dramatic metabolomic dysregulation than advanced infection stages. The metabolites identified are potential biological markers for the systemic physiological impact of AGD.

@article{
 title = {Prebiotic supplementation modulates selective effects of stress on behavior and brain metabolome in aged mice},
 type = {article},
 year = {2022},
 keywords = {Aging,Diet,Metabolome,Prebiotics,Stress},
 volume = {21},
 month = {11},
 publisher = {Elsevier Inc.},
 day = {1},
 id = {c1723eee-baa1-3796-8f13-d86e5a7530e3},
 created = {2025-07-07T13:25:40.643Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:24.432Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Aging has a significant impact on physiology with implications for central nervous system function coincident with increased vulnerability to stress exposures. A number of stress-sensitive molecular mechanisms are hypothesized to underpin age-related changes in brain function. Recent cumulative evidence also suggests that aging impacts gut microbiota composition. However, the impact of such effects on the ability of mammals to respond to stress in aging is still relatively unexplored. Therefore, in this study we assessed the ability of a microbiota-targeted intervention (the prebiotic FOS-Inulin) to alleviate age-related responses to stress. Exposure of aged C57BL/6 mice to social defeat led to an altered social interaction phenotype in the social interaction test, which was reversed by FOS-Inulin supplementation. Interestingly, this occured independent of affecting social defeat-induced elevations in the stress hormone corticosterone. Additionally, the behavioral modifications following FOS-Inulin supplementation were also not coincident with improvement of pro-inflammatory markers. Metabolomics analysis was performed and intriguingly, age associated metabolites were shown to be reduced in the prefrontal cortex of stressed aged mice and this deficit was recovered by FOS-Inulin supplementation. Taken together these results suggest that prebiotic dietary intervention rescued the behavioral response to stress in aged mice, not through amelioration of the inflammatory response, but by restoring the levels of key metabolites in the prefrontal cortex of aged animals. Therefore, dietary interventions could be a compelling avenue to improve the molecular and behavioral manifestations of chronic stress exposures in aging via targeting the microbiota-gut brain axis.},
 bibtype = {article},
 author = {Cruz-Pereira, Joana S. and Moloney, Gerard M. and Bastiaanssen, Thomaz F.S. and Boscaini, Serena and Tofani, Gabriel and Borras-Bisa, Julia and van de Wouw, Marcel and Fitzgerald, Patrick and Dinan, Timothy G. and Clarke, Gerard and Cryan, John F.},
 doi = {10.1016/j.ynstr.2022.100501},
 journal = {Neurobiology of Stress}
}

Aging has a significant impact on physiology with implications for central nervous system function coincident with increased vulnerability to stress exposures. A number of stress-sensitive molecular mechanisms are hypothesized to underpin age-related changes in brain function. Recent cumulative evidence also suggests that aging impacts gut microbiota composition. However, the impact of such effects on the ability of mammals to respond to stress in aging is still relatively unexplored. Therefore, in this study we assessed the ability of a microbiota-targeted intervention (the prebiotic FOS-Inulin) to alleviate age-related responses to stress. Exposure of aged C57BL/6 mice to social defeat led to an altered social interaction phenotype in the social interaction test, which was reversed by FOS-Inulin supplementation. Interestingly, this occured independent of affecting social defeat-induced elevations in the stress hormone corticosterone. Additionally, the behavioral modifications following FOS-Inulin supplementation were also not coincident with improvement of pro-inflammatory markers. Metabolomics analysis was performed and intriguingly, age associated metabolites were shown to be reduced in the prefrontal cortex of stressed aged mice and this deficit was recovered by FOS-Inulin supplementation. Taken together these results suggest that prebiotic dietary intervention rescued the behavioral response to stress in aged mice, not through amelioration of the inflammatory response, but by restoring the levels of key metabolites in the prefrontal cortex of aged animals. Therefore, dietary interventions could be a compelling avenue to improve the molecular and behavioral manifestations of chronic stress exposures in aging via targeting the microbiota-gut brain axis.

@article{
 title = {An online atlas of human plasma metabolite signatures of gut microbiome composition},
 type = {article},
 year = {2022},
 pages = {5370},
 volume = {13},
 websites = {https://www.medrxiv.org/content/10.1101/2021.12.23.21268179v1%0Ahttps://www.medrxiv.org/content/10.1101/2021.12.23.21268179v1.abstract,https://www.nature.com/articles/s41467-022-33050-0},
 month = {9},
 publisher = {Springer US},
 day = {23},
 id = {00a1d48e-aa5e-36d5-b74a-d5a61caf6bf0},
 created = {2025-07-07T13:25:40.970Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:24.818Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p -cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.},
 bibtype = {article},
 author = {Dekkers, Koen F. and Sayols-Baixeras, Sergi and Baldanzi, Gabriel and Nowak, Christoph and Hammar, Ulf and Nguyen, Diem and Varotsis, Georgios and Brunkwall, Louise and Nielsen, Nynne and Eklund, Aron C. and Bak Holm, Jacob and Nielsen, H. Bjørn and Ottosson, Filip and Lin, Yi-Ting and Ahmad, Shafqat and Lind, Lars and Sundström, Johan and Engström, Gunnar and Smith, J. Gustav and Ärnlöv, Johan and Orho-Melander, Marju and Fall, Tove},
 doi = {10.1038/s41467-022-33050-0},
 journal = {Nature Communications},
 number = {1}
}

Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p -cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.

@article{
 title = {Effects of an Amino Acid-Based Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety, and Gut Microbiome in Infants with Cow’s Milk Protein Allergy},
 type = {article},
 year = {2022},
 keywords = {2′-fucosyllactose,bifidobacteria,dysbiosis,gut microbiome,hypoallergenic formula,lacto-N-neotetraose,metagenomic sequencing,short chain fatty acids},
 volume = {14},
 month = {6},
 publisher = {MDPI},
 day = {1},
 id = {4f680e92-5bf5-354f-8ef1-8c92f0944836},
 created = {2025-10-30T12:05:02.949Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:19.630Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {This open-label, non-randomized, multicenter trial (Registration: NCT 03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow’s milk protein allergy (CMPA). Term infants aged 1–8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from –0.31 at the baseline to +0.28 at the 4-months’ follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.},
 bibtype = {article},
 author = {Gold, Michael S. and Quinn, Patrick J. and Campbell, Dianne E. and Peake, Jane and Smart, Joanne and Robinson, Marnie and O’sullivan, Michael and Vogt, Josef Korbinian and Pedersen, Helle Krogh and Liu, Xiaoqiu and Pazirandeh-Micol, Elham and Heine, Ralf G.},
 doi = {10.3390/NU14112297},
 journal = {Nutrients},
 number = {11}
}

This open-label, non-randomized, multicenter trial (Registration: NCT 03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow’s milk protein allergy (CMPA). Term infants aged 1–8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from –0.31 at the baseline to +0.28 at the 4-months’ follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.

@article{
 title = {Risk assessment with gut microbiome and metabolite markers in NAFLD development},
 type = {article},
 year = {2022},
 volume = {14},
 month = {6},
 publisher = {American Association for the Advancement of Science},
 day = {8},
 id = {e2f79dad-928d-3a59-b775-1b6c6267970e},
 created = {2025-10-30T12:05:02.950Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:02.950Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.},
 bibtype = {article},
 author = {Leung, Howell and Long, Xiaoxue and Ni, Yueqiong and Qian, Lingling and Nychas, Emmanouil and Siliceo, Sara Leal and Pohl, Dennis and Hanhineva, Kati and Liu, Yan and Xu, Aimin and Nielsen, Henrik B. and Belda, Eugeni and Clément, Karine and Loomba, Rohit and Li, Huating and Jia, Weiping and Panagiotou, Gianni},
 doi = {10.1126/SCITRANSLMED.ABK0855},
 journal = {Science Translational Medicine},
 number = {648}
}

A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.

@article{
 title = {Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial},
 type = {article},
 year = {2022},
 keywords = {Bifidobacterium longum subsp. infantis (B. infantis),Clostridioides (C.) difficile,bifidobacteria,gut maturation,gut microbiota,human milk oligosaccharides (HMOs),infant formula,intestinal immune response},
 volume = {9},
 month = {7},
 publisher = {Frontiers Media S.A.},
 day = {6},
 id = {432d7d70-fea7-3c2c-874e-6959178045d6},
 created = {2025-10-30T12:05:02.979Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:13.895Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Human milk oligosaccharides (HMOs) have important biological functions for a healthy development in early life. Objective: This study aimed to investigate gut maturation effects of an infant formula containing five HMOs (2′-fucosyllactose, 2′,3-di-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose, and 6′-sialyllactose). Methods: In a multicenter study, healthy infants (7–21 days old) were randomly assigned to a standard cow’s milk-based infant formula (control group, CG); the same formula with 1.5 g/L HMOs (test group 1, TG1); or with 2.5 g/L HMOs (test group 2, TG2). A human milk-fed group (HMG) was enrolled as a reference. Fecal samples collected at baseline (n∼150/formula group; HMG n = 60), age 3 (n∼140/formula group; HMG n = 65) and 6 (n∼115/formula group; HMG n = 60) months were analyzed for microbiome (shotgun metagenomics), metabolism, and biomarkers. Results: At both post-baseline visits, weighted UniFrac analysis indicated different microbiota compositions in the two test groups (TGs) compared to CG (P < 0.01) with coordinates closer to that of HMG. The relative abundance of Bifidobacterium longum subsp. infantis (B. infantis) was higher in TGs vs. CG (P < 0.05; except at 6 months: TG2 vs. CG P = 0.083). Bifidobacterium abundance was higher by ∼45% in TGs vs. CG at 6-month approaching HMG. At both post-baseline visits, toxigenic Clostridioides difficile abundance was 75–85% lower in TGs vs. CG (P < 0.05) and comparable with HMG. Fecal pH was significantly lower in TGs vs. CG, and the overall organic acid profile was different in TGs vs. CG, approaching HMG. At 3 months, TGs (vs. CG) had higher secretory immunoglobulin A (sIgA) and lower alpha-1-antitrypsin (P < 0.05). At 6 months, sIgA in TG2 vs. CG remained higher (P < 0.05), and calprotectin was lower in TG1 (P < 0.05) vs. CG. Conclusion: Infant formula with a specific blend of five HMOs supports the development of the intestinal immune system and gut barrier function and shifts the gut microbiome closer to that of breastfed infants with higher bifidobacteria, particularly B. infantis, and lower toxigenic Clostridioides difficile. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/], identifier [NCT03722550].},
 bibtype = {article},
 author = {Bosheva, Miroslava and Tokodi, Istvan and Krasnow, Aleksander and Pedersen, Helle Krogh and Lukjancenko, Oksana and Eklund, Aron C. and Grathwohl, Dominik and Sprenger, Norbert and Berger, Bernard and Cercamondi, Colin I.},
 doi = {10.3389/FNUT.2022.920362},
 journal = {Frontiers in Nutrition}
}

Background: Human milk oligosaccharides (HMOs) have important biological functions for a healthy development in early life. Objective: This study aimed to investigate gut maturation effects of an infant formula containing five HMOs (2′-fucosyllactose, 2′,3-di-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose, and 6′-sialyllactose). Methods: In a multicenter study, healthy infants (7–21 days old) were randomly assigned to a standard cow’s milk-based infant formula (control group, CG); the same formula with 1.5 g/L HMOs (test group 1, TG1); or with 2.5 g/L HMOs (test group 2, TG2). A human milk-fed group (HMG) was enrolled as a reference. Fecal samples collected at baseline (n∼150/formula group; HMG n = 60), age 3 (n∼140/formula group; HMG n = 65) and 6 (n∼115/formula group; HMG n = 60) months were analyzed for microbiome (shotgun metagenomics), metabolism, and biomarkers. Results: At both post-baseline visits, weighted UniFrac analysis indicated different microbiota compositions in the two test groups (TGs) compared to CG (P < 0.01) with coordinates closer to that of HMG. The relative abundance of Bifidobacterium longum subsp. infantis (B. infantis) was higher in TGs vs. CG (P < 0.05; except at 6 months: TG2 vs. CG P = 0.083). Bifidobacterium abundance was higher by ∼45% in TGs vs. CG at 6-month approaching HMG. At both post-baseline visits, toxigenic Clostridioides difficile abundance was 75–85% lower in TGs vs. CG (P < 0.05) and comparable with HMG. Fecal pH was significantly lower in TGs vs. CG, and the overall organic acid profile was different in TGs vs. CG, approaching HMG. At 3 months, TGs (vs. CG) had higher secretory immunoglobulin A (sIgA) and lower alpha-1-antitrypsin (P < 0.05). At 6 months, sIgA in TG2 vs. CG remained higher (P < 0.05), and calprotectin was lower in TG1 (P < 0.05) vs. CG. Conclusion: Infant formula with a specific blend of five HMOs supports the development of the intestinal immune system and gut barrier function and shifts the gut microbiome closer to that of breastfed infants with higher bifidobacteria, particularly B. infantis, and lower toxigenic Clostridioides difficile. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/], identifier [NCT03722550].

@article{
 title = {Host–microbial co-metabolites modulated by human milk oligosaccharides relate to reduced risk of respiratory tract infections},
 type = {article},
 year = {2022},
 keywords = {gut microbiome,metabolites,milk oligosaccharides,pediatric nutrition,respiratory infection},
 volume = {9},
 month = {8},
 publisher = {Frontiers Media S.A.},
 day = {4},
 id = {216d4dca-8085-3cdc-bbf5-6262fdb99dcd},
 created = {2025-10-30T12:05:02.982Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:07.531Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Human milk oligosaccharides (HMOs) are structurally diverse oligosaccharides present in breast milk, supporting the development of the gut microbiota and immune system. Previously, 2-HMO (2'fucosyllactose, lacto-N-neotetraose) compared to control formula feeding was associated with reduced risk of lower respiratory tract infections (LRTIs), in part linked to lower acetate and higher bifidobacteria proportions. Here, our objective was to gain further insight into additional molecular pathways linking the 2-HMO formula feeding and LRTI mitigation. From the same trial, we measured the microbiota composition and 743 known biochemical species in infant stool at 3 months of age using shotgun metagenomic sequencing and untargeted mass spectrometry metabolomics. We used multivariate analysis to identify biochemicals associated to 2-HMO formula feeding and LRTI and integrated those findings with the microbiota compositional data. Three molecular pathways stood out: increased gamma-glutamylation and N-acetylation of amino acids and decreased inflammatory signaling lipids. Integration of stool metagenomic data revealed some Bifidobacterium and Bacteroides species to be implicated. These findings deepen our understanding of the infant gut/microbiome co-metabolism in early life and provide evidence for how such metabolic changes may influence immune competence at distant mucosal sites such as the airways.},
 bibtype = {article},
 author = {Martin, François Pierre and Tytgat, Hanne L.P. and Krogh Pedersen, Helle and Moine, Deborah and Eklund, Aron C. and Berger, Bernard and Sprenger, Norbert},
 doi = {10.3389/FNUT.2022.935711},
 journal = {Frontiers in Nutrition}
}

Human milk oligosaccharides (HMOs) are structurally diverse oligosaccharides present in breast milk, supporting the development of the gut microbiota and immune system. Previously, 2-HMO (2'fucosyllactose, lacto-N-neotetraose) compared to control formula feeding was associated with reduced risk of lower respiratory tract infections (LRTIs), in part linked to lower acetate and higher bifidobacteria proportions. Here, our objective was to gain further insight into additional molecular pathways linking the 2-HMO formula feeding and LRTI mitigation. From the same trial, we measured the microbiota composition and 743 known biochemical species in infant stool at 3 months of age using shotgun metagenomic sequencing and untargeted mass spectrometry metabolomics. We used multivariate analysis to identify biochemicals associated to 2-HMO formula feeding and LRTI and integrated those findings with the microbiota compositional data. Three molecular pathways stood out: increased gamma-glutamylation and N-acetylation of amino acids and decreased inflammatory signaling lipids. Integration of stool metagenomic data revealed some Bifidobacterium and Bacteroides species to be implicated. These findings deepen our understanding of the infant gut/microbiome co-metabolism in early life and provide evidence for how such metabolic changes may influence immune competence at distant mucosal sites such as the airways.

@article{
 title = {Distinct infant feeding type-specific plasma metabolites at age 3 months associate with body composition at 2 years},
 type = {article},
 year = {2022},
 keywords = {Adiposity,Body composition,Breastfeeding,Metabolomics},
 pages = {1290-1296},
 volume = {41},
 month = {6},
 publisher = {Churchill Livingstone},
 day = {1},
 id = {f1ab488c-bf73-31c8-b175-71807e9cbab1},
 created = {2025-10-30T12:05:02.985Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:05.964Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background & objectives: Early life is a critical window for adiposity programming and metabolic profile may affect this programming. We investigated if plasma metabolites at age 3 months were associated with fat mass, fat free mass and abdominal subcutaneous and visceral fat outcomes at age 2 years in a cohort of healthy infants and if these associations were different between infants receiving exclusive breastfeeding (EBF) and those with exclusive formula feeding (EFF). Methods: In 318 healthy term-born infants, we determined body composition by Dual Energy X-ray absorptiometry (DXA) and visceral fat by abdominal ultrasound at 2 age years. High-throughput metabolic profiling was performed on blood samples collected at age 3 months. Tertiles were generated for each body composition outcome and differences in plasma metabolite levels at age 3 months between infants with high and low body composition outcomes at age 2 years were evaluated in general, as well as separately in EBF- and EFF-infants. Results: Distinct plasma metabolite variables identified at age 3 months were associated with body composition at 2 years. These metabolites included several classes of lyso-phospholipids. Associations between the metabolites at age 3 months and fat mass index, fat mass percentage, fat free mass index and visceral fat at 2 years were predominantly found in EBF-infants. Conclusion: Associations between plasma metabolite levels at age 3 months and high body fat mass at 2 years depend on infant feeding type. These findings contribute to our insight into the importance of infant feeding on adiposity programming in early life.},
 bibtype = {article},
 author = {van Beijsterveldt, Inge A.L.P. and Myers, Pernille Neve and Snowden, Stuart G. and Ong, Ken K. and Brix, Susanne and Hokken-Koelega, Anita C.S. and Koulman, Albert},
 doi = {10.1016/J.CLNU.2022.04.015},
 journal = {Clinical Nutrition},
 number = {6}
}

Background & objectives: Early life is a critical window for adiposity programming and metabolic profile may affect this programming. We investigated if plasma metabolites at age 3 months were associated with fat mass, fat free mass and abdominal subcutaneous and visceral fat outcomes at age 2 years in a cohort of healthy infants and if these associations were different between infants receiving exclusive breastfeeding (EBF) and those with exclusive formula feeding (EFF). Methods: In 318 healthy term-born infants, we determined body composition by Dual Energy X-ray absorptiometry (DXA) and visceral fat by abdominal ultrasound at 2 age years. High-throughput metabolic profiling was performed on blood samples collected at age 3 months. Tertiles were generated for each body composition outcome and differences in plasma metabolite levels at age 3 months between infants with high and low body composition outcomes at age 2 years were evaluated in general, as well as separately in EBF- and EFF-infants. Results: Distinct plasma metabolite variables identified at age 3 months were associated with body composition at 2 years. These metabolites included several classes of lyso-phospholipids. Associations between the metabolites at age 3 months and fat mass index, fat mass percentage, fat free mass index and visceral fat at 2 years were predominantly found in EBF-infants. Conclusion: Associations between plasma metabolite levels at age 3 months and high body fat mass at 2 years depend on infant feeding type. These findings contribute to our insight into the importance of infant feeding on adiposity programming in early life.

@article{
 title = {Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient: a case report},
 type = {article},
 year = {2022},
 keywords = {Clostridioides difficile infection,Engraftment,Fecal microbiota transplantation,Gut microbiota,Infant,Neonatal seeding,Pregnancy,Strain transfer},
 volume = {10},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {599b9b9a-2d80-313d-81f0-efedacdde4d0},
 created = {2025-10-30T12:05:02.992Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:12.494Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment. Methods: A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults. Results: The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient’s gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer. Conclusions: The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. [MediaObject not available: see fulltext.]},
 bibtype = {article},
 author = {Wei, Shaodong and Jespersen, Marie Louise and Baunwall, Simon Mark Dahl and Myers, Pernille Neve and Smith, Emilie Milton and Dahlerup, Jens Frederik and Rasmussen, Simon and Nielsen, Henrik Bjørn and Licht, Tine Rask and Bahl, Martin Iain and Hvas, Christian Lodberg},
 doi = {10.1186/S40168-022-01394-W},
 journal = {Microbiome},
 number = {1}
}

Background: Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment. Methods: A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults. Results: The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient’s gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer. Conclusions: The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. [MediaObject not available: see fulltext.]

@article{
 title = {Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population},
 type = {article},
 year = {2022},
 pages = {297-308},
 volume = {76},
 month = {2},
 publisher = {Springer Nature},
 day = {1},
 id = {ea7dde87-52da-3fe9-9ab3-0dd5d45dba13},
 created = {2025-10-30T12:05:02.996Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:07.984Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Urolithin A (UA) is produced by gut microflora from foods rich in ellagitannins. UA has been shown to improve mitochondrial health preclinically and in humans. Not everyone has a microbiome capable of producing UA, making supplementation with UA an appealing strategy. Objective: This is the first detailed investigation of the prevalence of UA producers in a healthy population and the ability of direct UA supplementation to overcome both microbiome and dietary variability. Dietary intake of a glass of pomegranate juice (PJ) was used to assess UA producer status (n = 100 participants) and to characterize differences in gut microbiome between UA producers from non-producers. Methods: Subjects were randomized (1:1) to either PJ or a food product containing UA (500 mg). Prevalence of UA producers and non-producers were determined in the PJ group. Diet questionnaires and fecal samples were collected to compare differences between UA producers and non-producers along with plasma samples at different time points to assess levels of UA and its conjugates between the interventions. Results: Only 12% of subjects had detectable levels of UA at baseline. Following PJ intake ~40% of the subjects converted significantly the precursor compounds into UA. UA producers were distinguished by a significantly higher gut microbiome diversity and ratio of Firmicutes to Bacteroides. Direct supplementation with UA significantly increased plasma levels and provided a >6-fold exposure to UA vs. PJ (p < 0.0001). Conclusions: Differences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation.},
 bibtype = {article},
 author = {Singh, Anurag and D’Amico, Davide and Andreux, Pénélope A. and Dunngalvin, Gillian and Kern, Timo and Blanco-Bose, William and Auwerx, Johan and Aebischer, Patrick and Rinsch, Chris},
 doi = {10.1038/S41430-021-00950-1},
 journal = {European Journal of Clinical Nutrition},
 number = {2}
}

Background: Urolithin A (UA) is produced by gut microflora from foods rich in ellagitannins. UA has been shown to improve mitochondrial health preclinically and in humans. Not everyone has a microbiome capable of producing UA, making supplementation with UA an appealing strategy. Objective: This is the first detailed investigation of the prevalence of UA producers in a healthy population and the ability of direct UA supplementation to overcome both microbiome and dietary variability. Dietary intake of a glass of pomegranate juice (PJ) was used to assess UA producer status (n = 100 participants) and to characterize differences in gut microbiome between UA producers from non-producers. Methods: Subjects were randomized (1:1) to either PJ or a food product containing UA (500 mg). Prevalence of UA producers and non-producers were determined in the PJ group. Diet questionnaires and fecal samples were collected to compare differences between UA producers and non-producers along with plasma samples at different time points to assess levels of UA and its conjugates between the interventions. Results: Only 12% of subjects had detectable levels of UA at baseline. Following PJ intake ~40% of the subjects converted significantly the precursor compounds into UA. UA producers were distinguished by a significantly higher gut microbiome diversity and ratio of Firmicutes to Bacteroides. Direct supplementation with UA significantly increased plasma levels and provided a >6-fold exposure to UA vs. PJ (p < 0.0001). Conclusions: Differences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation.

@article{
 title = {Vaginal microbiome following orally administered probiotic},
 type = {article},
 year = {2022},
 keywords = {Vaginal microbiome,healthy microbiome,public health,shotgun metagenomics,women},
 pages = {605-611},
 volume = {130},
 month = {10},
 publisher = {John Wiley and Sons Inc},
 day = {1},
 id = {aa7445bf-8fb5-34a6-b5bd-3c19780102ba},
 created = {2025-10-30T12:05:03.013Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.013Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Here, we present a longitudinal shotgun sequencing metagenomics study of 16 healthy, Danish women in the reproductive age. The aim of the study was to investigate whether lactobacilli, orally consumed, had any impact on the vaginal microbiome and its functional potential. The 16 women aged 19–45 years were recruited from Copenhagen, Denmark. One baseline vaginal sample (Day 0) and two study samples (Days 25–30 and Days 55–60, respectively), were sampled. The vaginal samples were analyzed by shotgun metagenomics. We detected 26 species in the vaginal microbiota of the 16 women, of which six belonged to the Lactobacillus genus. We observed three vaginal microbiome clusters mainly dominated by Gardnerella vaginalis, Lactobacillus iners, or Lactobacillus crispatus. The oral probiotic had no detectable effect on either the composition or the functional potential of the vaginal microbiota. Most of the study subjects (11 out of 16 women) exhibited only minor changes in the vaginal microbiome during the treatment with probiotics. Any compositional changes could not be associated to the probiotic treatment. Future studies may benefit from an increased number of participants, and administration of the probiotics during conditions with bacterial imbalance (e.g., during/after antibiotic treatment) or the use of different Lactobacillus spp. known to colonize the vagina.},
 bibtype = {article},
 author = {Hertz, Frederik Boetius and Holm, Jacob Bak and Pallejá, Albert and Björnsdóttir, María Kristín and Mikkelsen, Lasse Sommer and Brandsborg, Erik and Frimodt-Møller, Niels},
 doi = {10.1111/APM.13261},
 journal = {APMIS},
 number = {10}
}

Here, we present a longitudinal shotgun sequencing metagenomics study of 16 healthy, Danish women in the reproductive age. The aim of the study was to investigate whether lactobacilli, orally consumed, had any impact on the vaginal microbiome and its functional potential. The 16 women aged 19–45 years were recruited from Copenhagen, Denmark. One baseline vaginal sample (Day 0) and two study samples (Days 25–30 and Days 55–60, respectively), were sampled. The vaginal samples were analyzed by shotgun metagenomics. We detected 26 species in the vaginal microbiota of the 16 women, of which six belonged to the Lactobacillus genus. We observed three vaginal microbiome clusters mainly dominated by Gardnerella vaginalis, Lactobacillus iners, or Lactobacillus crispatus. The oral probiotic had no detectable effect on either the composition or the functional potential of the vaginal microbiota. Most of the study subjects (11 out of 16 women) exhibited only minor changes in the vaginal microbiome during the treatment with probiotics. Any compositional changes could not be associated to the probiotic treatment. Future studies may benefit from an increased number of participants, and administration of the probiotics during conditions with bacterial imbalance (e.g., during/after antibiotic treatment) or the use of different Lactobacillus spp. known to colonize the vagina.

@article{
 title = {Towards the biogeography of prokaryotic genes},
 type = {article},
 year = {2022},
 pages = {252-256},
 volume = {601},
 month = {1},
 publisher = {Nature Research},
 day = {13},
 id = {7840468a-3fb6-34c3-99bf-d8e65d5d56d4},
 created = {2025-10-30T12:05:03.032Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.032Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Microbial genes encode the majority of the functional repertoire of life on earth. However, despite increasing efforts in metagenomic sequencing of various habitats1–3, little is known about the distribution of genes across the global biosphere, with implications for human and planetary health. Here we constructed a non-redundant gene catalogue of 303 million species-level genes (clustered at 95% nucleotide identity) from 13,174 publicly available metagenomes across 14 major habitats and use it to show that most genes are specific to a single habitat. The small fraction of genes found in multiple habitats is enriched in antibiotic-resistance genes and markers for mobile genetic elements. By further clustering these species-level genes into 32 million protein families, we observed that a small fraction of these families contain the majority of the genes (0.6% of families account for 50% of the genes). The majority of species-level genes and protein families are rare. Furthermore, species-level genes, and in particular the rare ones, show low rates of positive (adaptive) selection, supporting a model in which most genetic variability observed within each protein family is neutral or nearly neutral.},
 bibtype = {article},
 author = {Coelho, Luis Pedro and Alves, Renato and del Río, Álvaro Rodríguez and Myers, Pernille Neve and Cantalapiedra, Carlos P. and Giner-Lamia, Joaquín and Schmidt, Thomas Sebastian and Mende, Daniel R. and Orakov, Askarbek and Letunic, Ivica and Hildebrand, Falk and Van Rossum, Thea and Forslund, Sofia K. and Khedkar, Supriya and Maistrenko, Oleksandr M. and Pan, Shaojun and Jia, Longhao and Ferretti, Pamela and Sunagawa, Shinichi and Zhao, Xing Ming and Nielsen, Henrik Bjørn and Huerta-Cepas, Jaime and Bork, Peer},
 doi = {10.1038/S41586-021-04233-4},
 journal = {Nature},
 number = {7892}
}

Microbial genes encode the majority of the functional repertoire of life on earth. However, despite increasing efforts in metagenomic sequencing of various habitats1–3, little is known about the distribution of genes across the global biosphere, with implications for human and planetary health. Here we constructed a non-redundant gene catalogue of 303 million species-level genes (clustered at 95% nucleotide identity) from 13,174 publicly available metagenomes across 14 major habitats and use it to show that most genes are specific to a single habitat. The small fraction of genes found in multiple habitats is enriched in antibiotic-resistance genes and markers for mobile genetic elements. By further clustering these species-level genes into 32 million protein families, we observed that a small fraction of these families contain the majority of the genes (0.6% of families account for 50% of the genes). The majority of species-level genes and protein families are rare. Furthermore, species-level genes, and in particular the rare ones, show low rates of positive (adaptive) selection, supporting a model in which most genetic variability observed within each protein family is neutral or nearly neutral.

@article{
 title = {Patients with psoriasis have a dysbiotic taxonomic and functional gut microbiota*},
 type = {article},
 year = {2022},
 pages = {89-98},
 volume = {187},
 month = {7},
 publisher = {John Wiley and Sons Inc},
 day = {1},
 id = {0acae7bd-bacf-34a3-a970-92604ef6cde8},
 created = {2025-10-30T12:05:03.032Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.032Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Accumulating evidence supports the findings of an altered gut microbiota in patients with autoimmune disease. However, existing studies on the role of the gut microbiota in patients with psoriasis have demonstrated conflicting results and have mainly been based on 16s rRNA gene sequencing analysis. Objectives: To examine whether the gut microbiota of patients with psoriasis was altered in composition and functional potentials compared with healthy controls, and as a second approach compared with healthy cohabitant partners. A further aim was to investigate relationships to disease severity, and seasonal impact on the gut microbiota. Methods: In a case–control study, 126 faecal samples were collected from a sample of 53 systemically untreated patients with plaque psoriasis; 52 healthy controls matched for age, sex and body mass index; and 21 cohabitant partners. A subpopulation of 18 patients with psoriasis and 19 healthy controls continued in a longitudinal study, where four to six faecal samples were collected over 9–12 months. The gut microbiota was characterized using shotgun metagenomic sequencing analysis. Results: A significantly lower richness (P = 0·007) and difference in community composition (P = 0·01) of metagenomic species was seen in patients with psoriasis compared with healthy controls, and patients with psoriasis had a lower microbial diversity than their partners (P = 0·04). Additionally, the functional richness was decreased in patients with psoriasis compared with healthy controls (P = 0·01) and partners (P = 0·05). Increased disease severity was correlated with alterations in taxonomy and function, with a slight tendency towards a lower richness of metagenomic species, albeit not significant (P = 0·08). The seasonal analysis showed no shifts in community composition in healthy controls or in patients with psoriasis. Conclusions: The findings of a different gut microbiota in composition and functional potentials between patients with psoriasis and healthy controls support a linkage between the gut microbiota and psoriasis. These findings need to be validated in larger studies, and a potential causal relationship between the gut microbiota and psoriasis still needs to be shown.},
 bibtype = {article},
 author = {Todberg, Tanja and Egeberg, Alexander and Zachariae, Claus and Sørensen, Nikolaj and Pedersen, Oluf and Skov, Lone},
 doi = {10.1111/BJD.21245},
 journal = {British Journal of Dermatology},
 number = {1}
}

Background: Accumulating evidence supports the findings of an altered gut microbiota in patients with autoimmune disease. However, existing studies on the role of the gut microbiota in patients with psoriasis have demonstrated conflicting results and have mainly been based on 16s rRNA gene sequencing analysis. Objectives: To examine whether the gut microbiota of patients with psoriasis was altered in composition and functional potentials compared with healthy controls, and as a second approach compared with healthy cohabitant partners. A further aim was to investigate relationships to disease severity, and seasonal impact on the gut microbiota. Methods: In a case–control study, 126 faecal samples were collected from a sample of 53 systemically untreated patients with plaque psoriasis; 52 healthy controls matched for age, sex and body mass index; and 21 cohabitant partners. A subpopulation of 18 patients with psoriasis and 19 healthy controls continued in a longitudinal study, where four to six faecal samples were collected over 9–12 months. The gut microbiota was characterized using shotgun metagenomic sequencing analysis. Results: A significantly lower richness (P = 0·007) and difference in community composition (P = 0·01) of metagenomic species was seen in patients with psoriasis compared with healthy controls, and patients with psoriasis had a lower microbial diversity than their partners (P = 0·04). Additionally, the functional richness was decreased in patients with psoriasis compared with healthy controls (P = 0·01) and partners (P = 0·05). Increased disease severity was correlated with alterations in taxonomy and function, with a slight tendency towards a lower richness of metagenomic species, albeit not significant (P = 0·08). The seasonal analysis showed no shifts in community composition in healthy controls or in patients with psoriasis. Conclusions: The findings of a different gut microbiota in composition and functional potentials between patients with psoriasis and healthy controls support a linkage between the gut microbiota and psoriasis. These findings need to be validated in larger studies, and a potential causal relationship between the gut microbiota and psoriasis still needs to be shown.

@article{
 title = {Effects of addition of 2-fucosyllactose to infant formula on growth and specific pathways of utilization by Bifidobacterium in healthy term infants},
 type = {article},
 year = {2022},
 keywords = {bifidobacteria,fucosyllactose,gene expression,growth,infant formula},
 volume = {9},
 month = {9},
 publisher = {Frontiers Media S.A.},
 day = {23},
 id = {ed8f8064-0f26-3aa3-849b-dfe50c866165},
 created = {2025-10-30T12:05:03.033Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:08.503Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Oligosaccharides in human milk support health via intestinal microbiome. We studied effects of addition of 2-fucosyllactose (2′FL) to the infant formula on infant growth, occurrence of adverse events (AE), and infant microbiome, including expression of microbial genes that metabolize 2′FL. Our hypothesis was that while 2′FL would not affect growth, it would cause changes in microbiome metabolism. In a double-blinded randomized controlled study fashion, the infant formula ± 2′FL or human milk was fed to healthy term infants for 16 weeks. Fecal samples obtained at baseline and week 16 were analyzed for microbial populations, metagenomic species concept (MGS), and genetics of gut metabolic modules (GMMs). There were no effects of addition of 2′FL on growth or AEs. There were no significant differences by feeding group in MGS richness or Shannon diversity at baseline, but formula groups each had significantly greater richness (p < 0.05) and diversity (p < 0.05) after 16 weeks of feeding than the breastfed group. While two glycosyl hydrolase (GH) families (GH42 and GH112) were significantly increased, two other GH families (GH20 and GH2) were significantly decreased in the test formula group compared to the control formula group; although modest, addition of 2′FL resulted in changes in microbiome in the direction of breastfed infants, consistent with internal metabolism of HMOs by Bifidobacterium.},
 bibtype = {article},
 author = {Wallingford, John C. and Neve Myers, Pernille and Barber, Cynthia M.},
 doi = {10.3389/FNUT.2022.961526},
 journal = {Frontiers in Nutrition}
}

Oligosaccharides in human milk support health via intestinal microbiome. We studied effects of addition of 2-fucosyllactose (2′FL) to the infant formula on infant growth, occurrence of adverse events (AE), and infant microbiome, including expression of microbial genes that metabolize 2′FL. Our hypothesis was that while 2′FL would not affect growth, it would cause changes in microbiome metabolism. In a double-blinded randomized controlled study fashion, the infant formula ± 2′FL or human milk was fed to healthy term infants for 16 weeks. Fecal samples obtained at baseline and week 16 were analyzed for microbial populations, metagenomic species concept (MGS), and genetics of gut metabolic modules (GMMs). There were no effects of addition of 2′FL on growth or AEs. There were no significant differences by feeding group in MGS richness or Shannon diversity at baseline, but formula groups each had significantly greater richness (p < 0.05) and diversity (p < 0.05) after 16 weeks of feeding than the breastfed group. While two glycosyl hydrolase (GH) families (GH42 and GH112) were significantly increased, two other GH families (GH20 and GH2) were significantly decreased in the test formula group compared to the control formula group; although modest, addition of 2′FL resulted in changes in microbiome in the direction of breastfed infants, consistent with internal metabolism of HMOs by Bifidobacterium.

@article{
 title = {Distinct Diet-Microbiota-Metabolism Interactions in Overweight and Obese Pregnant Women: a Metagenomics Approach},
 type = {article},
 year = {2022},
 volume = {10},
 month = {4},
 publisher = {American Society for Microbiology},
 day = {27},
 id = {95fbfcc4-358c-3314-b788-a0fce8497c08},
 created = {2025-10-30T12:05:03.037Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:10.697Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = { We observed partially distinct diet-gut microbiota-metabolism and inflammation responses in overweight and obese pregnant women. In overweight women, gut microbiota community composition and the relative abundance of A. finegoldii were associated with an inflammatory status. In obese women, a higher dietary quality was related to a higher gut microbiota diversity and a healthy inflammatory status.  Diet and gut microbiota are known to modulate metabolic health. Our aim was to apply a metagenomics approach to investigate whether the diet-gut microbiota-metabolism and inflammation relationships differ in pregnant overweight and obese women. This cross-sectional study was conducted in overweight ( n = 234) and obese ( n = 152) women during early pregnancy. Dietary quality was measured by a validated index of diet quality (IDQ). Gut microbiota taxonomic composition and species diversity were assessed by metagenomic profiling (Illumina HiSeq platform). Markers for glucose metabolism (glucose, insulin) and low-grade inflammation (high sensitivity C-reactive protein [hsCRP], glycoprotein acetylation [GlycA]) were analyzed from blood samples. Higher IDQ scores were positively associated with a higher gut microbiota species diversity ( r = 0.273, P  = 0.007) in obese women, but not in overweight women. Community composition (beta diversity) was associated with the GlycA level in the overweight women ( P  = 0.04) but not in the obese. Further analysis at the species level revealed a positive association between the abundance of species Alistipes finegoldii and the GlycA level in overweight women (logfold change = 4.74, P  = 0.04). This study has been registered at ClinicalTrials.gov under registration no. NCT01922791 ( https://clinicaltrials.gov/ct2/show/NCT01922791 ).  IMPORTANCE We observed partially distinct diet-gut microbiota-metabolism and inflammation responses in overweight and obese pregnant women. In overweight women, gut microbiota community composition and the relative abundance of A. finegoldii were associated with an inflammatory status. In obese women, a higher dietary quality was related to a higher gut microbiota diversity and a healthy inflammatory status. },
 bibtype = {article},
 author = {Lotankar, Mrunalini and Mokkala, Kati and Houttu, Noora and Koivuniemi, Ella and Sørensen, Nikolaj and Nielsen, Henrik Bjørn and Munukka, Eveliina and Lahti, Leo and Laitinen, Kirsi},
 doi = {10.1128/SPECTRUM.00893-21},
 journal = {Microbiology Spectrum},
 number = {2}
}

We observed partially distinct diet-gut microbiota-metabolism and inflammation responses in overweight and obese pregnant women. In overweight women, gut microbiota community composition and the relative abundance of A. finegoldii were associated with an inflammatory status. In obese women, a higher dietary quality was related to a higher gut microbiota diversity and a healthy inflammatory status. Diet and gut microbiota are known to modulate metabolic health. Our aim was to apply a metagenomics approach to investigate whether the diet-gut microbiota-metabolism and inflammation relationships differ in pregnant overweight and obese women. This cross-sectional study was conducted in overweight ( n = 234) and obese ( n = 152) women during early pregnancy. Dietary quality was measured by a validated index of diet quality (IDQ). Gut microbiota taxonomic composition and species diversity were assessed by metagenomic profiling (Illumina HiSeq platform). Markers for glucose metabolism (glucose, insulin) and low-grade inflammation (high sensitivity C-reactive protein [hsCRP], glycoprotein acetylation [GlycA]) were analyzed from blood samples. Higher IDQ scores were positively associated with a higher gut microbiota species diversity ( r = 0.273, P = 0.007) in obese women, but not in overweight women. Community composition (beta diversity) was associated with the GlycA level in the overweight women ( P = 0.04) but not in the obese. Further analysis at the species level revealed a positive association between the abundance of species Alistipes finegoldii and the GlycA level in overweight women (logfold change = 4.74, P = 0.04). This study has been registered at ClinicalTrials.gov under registration no. NCT01922791 ( https://clinicaltrials.gov/ct2/show/NCT01922791 ). IMPORTANCE We observed partially distinct diet-gut microbiota-metabolism and inflammation responses in overweight and obese pregnant women. In overweight women, gut microbiota community composition and the relative abundance of A. finegoldii were associated with an inflammatory status. In obese women, a higher dietary quality was related to a higher gut microbiota diversity and a healthy inflammatory status.

@article{
 title = {Metabolomics in early life and the association with body composition at age 2 years},
 type = {article},
 year = {2022},
 keywords = {adiposity,body composition,infants,metabolomics,skinfolds},
 volume = {17},
 month = {3},
 publisher = {John Wiley and Sons Ltd},
 day = {1},
 id = {2676cb50-ccd1-39b5-95e5-650bd399322a},
 created = {2025-10-30T12:05:03.037Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.037Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background and Objectives: Early life is a critical window for adiposity programming. Metabolic-profile in early life may reflect this programming and correlate with later life adiposity. We investigated if metabolic-profile at 3 months of age is predictive for body composition at 2 years and if there are differences between boys and girls and between infant feeding types. Methods: In 318 healthy term-born infants, we determined body composition with skinfold measurements and abdominal ultrasound at 3 months and 2 years of age. High-throughput-metabolic-profiling was performed on 3-month-blood-samples. Using random-forest-machine-learning-models, we studied if the metabolic-profile at 3 months can predict body composition outcomes at 2 years of age. Results: Plasma metabolite-profile at 3 months was found to predict body composition at 2 years, based on truncal: peripheral-fat-skinfold-ratio (T:P-ratio), with a predictive value of 75.8%, sensitivity of 100% and specificity of 50%. Predictive value was higher in boys (Q2 = 0.322) than girls (Q2 = 0.117). Of the 15 metabolite variables most strongly associated with T:P-ratio, 11 were also associated with visceral fat at 2 years of age. Conclusion: Several plasma metabolites (LysoPC(22:2), dimethylarginine and others) at 3 months associate with body composition outcome at 2 years. These results highlight the importance of the first months of life for adiposity programming.},
 bibtype = {article},
 author = {van Beijsterveldt, Inge A.L.P. and Snowden, Stuart G. and Myers, Pernille Neve and de Fluiter, Kirsten S. and van de Heijning, Bert and Brix, Susanne and Ong, Ken K. and Dunger, David B. and Hokken-Koelega, Anita C.S. and Koulman, Albert},
 doi = {10.1111/IJPO.12859},
 journal = {Pediatric Obesity},
 number = {3}
}

Background and Objectives: Early life is a critical window for adiposity programming. Metabolic-profile in early life may reflect this programming and correlate with later life adiposity. We investigated if metabolic-profile at 3 months of age is predictive for body composition at 2 years and if there are differences between boys and girls and between infant feeding types. Methods: In 318 healthy term-born infants, we determined body composition with skinfold measurements and abdominal ultrasound at 3 months and 2 years of age. High-throughput-metabolic-profiling was performed on 3-month-blood-samples. Using random-forest-machine-learning-models, we studied if the metabolic-profile at 3 months can predict body composition outcomes at 2 years of age. Results: Plasma metabolite-profile at 3 months was found to predict body composition at 2 years, based on truncal: peripheral-fat-skinfold-ratio (T:P-ratio), with a predictive value of 75.8%, sensitivity of 100% and specificity of 50%. Predictive value was higher in boys (Q2 = 0.322) than girls (Q2 = 0.117). Of the 15 metabolite variables most strongly associated with T:P-ratio, 11 were also associated with visceral fat at 2 years of age. Conclusion: Several plasma metabolites (LysoPC(22:2), dimethylarginine and others) at 3 months associate with body composition outcome at 2 years. These results highlight the importance of the first months of life for adiposity programming.

@article{
 title = {Successful treatment of psoriasis with adalimumab induced no changes in the gut microbiota},
 type = {article},
 year = {2022},
 pages = {e464-e467},
 volume = {36},
 month = {6},
 publisher = {John Wiley and Sons Inc},
 day = {1},
 id = {858f4137-3bcd-3d84-8958-394132f8deba},
 created = {2025-10-30T12:05:03.041Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.041Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Todberg, T. and Egeberg, A. and Zachariae, C. and Sørensen, N. and Pedersen, O. and Skov, L.},
 doi = {10.1111/JDV.17952},
 journal = {Journal of the European Academy of Dermatology and Venereology},
 number = {6}
}

@article{
 title = {An online atlas of human plasma metabolite signatures of gut microbiome composition},
 type = {article},
 year = {2022},
 volume = {13},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {010c9715-6a9e-3959-b5a6-0a15fd618cd6},
 created = {2025-10-30T12:05:03.061Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:10.394Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas (https://gutsyatlas.serve.scilifelab.se/). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.},
 bibtype = {article},
 author = {Dekkers, Koen F. and Sayols-Baixeras, Sergi and Baldanzi, Gabriel and Nowak, Christoph and Hammar, Ulf and Nguyen, Diem and Varotsis, Georgios and Brunkwall, Louise and Nielsen, Nynne and Eklund, Aron C. and Bak Holm, Jacob and Nielsen, H. Bjørn and Ottosson, Filip and Lin, Yi Ting and Ahmad, Shafqat and Lind, Lars and Sundström, Johan and Engström, Gunnar and Smith, J. Gustav and Ärnlöv, Johan and Orho-Melander, Marju and Fall, Tove},
 doi = {10.1038/S41467-022-33050-0},
 journal = {Nature Communications},
 number = {1}
}

Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas (https://gutsyatlas.serve.scilifelab.se/). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.

@article{
 title = {A Changed Gut Microbiota Diversity Is Associated With Metabolic Improvements After Duodenal Mucosal Resurfacing With Glucagon-Like-Peptide-1 Receptor Agonist in Type 2 Diabetes in a Pilot Study},
 type = {article},
 year = {2022},
 keywords = {DMR,GLP-1RA,diabetes type 2,duodenal mucosal resurfacing,endoscopic,gut microbiota,microbiota diversity},
 volume = {3},
 publisher = {Frontiers Media SA},
 id = {d08cad26-224b-3c1c-b72f-6c2977899c32},
 created = {2025-10-30T12:05:03.064Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:08.181Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction: The gut microbiota influences and interacts with the host metabolism through effects on nutrient metabolism and digestion. Duodenal Mucosal Resurfacing (DMR) is a novel endoscopic procedure involving duodenal mucosal ablation by the use of hydrothermal energy. DMR, when combined with a glucagon-like peptide-1 receptor agonist (GLP-1RA), resulted in discontinuation of exogenous insulin treatment in 69% of patients with insulin dependent type 2 diabetes mellitus (T2DM) in the INSPIRE study. These patients also experienced improved glycaemic control and metabolic health. We thus investigated if these clinical effects were associated with a change in gut microbiota alpha and beta diversity. Methods: Faecal samples from the 16 patients were obtained for Illumina shotgun sequencing at baseline and 3 months after DMR. We assessed alpha and beta diversity of the gut microbiota in these samples and analysed its correlations with changes in HbA1c, body weight, and liver MRI proton density fat fraction (PDFF). Results: HbA1c correlated negatively with alpha diversity (p=0.011, rho: -0.62) whereas changes in PDFF correlated significantly with beta diversity (p=0.036, rho: 0.55) 3 months after initiation of the combined intervention. These correlations with metabolic parameters were observed despite finding no change in gut microbiota diversity at 3 months post DMR. Discussion: The correlation between gut microbiota richness (alpha diversity) and HbA1c as well as the change in PDFF and changed microbiota composition (beta diversity) suggests that changed gut microbiota diversity is associated with metabolic improvements after DMR in combination with glucagon-like-peptide-1 receptor agonist in type 2 diabetes. Larger controlled studies are however needed to find causal links between DMR with GLP-1RA, the gut microbiota, and improvements in metabolic health.},
 bibtype = {article},
 author = {Meiring, Suzanne and van Baar, Annieke C.G. and Sørensen, Nikolaj and Holleman, Frits and Soeters, Maarten R. and Nieuwdorp, Max and Bergman, Jacques J.G.H.M.},
 doi = {10.3389/FCDHC.2022.856661},
 journal = {Frontiers in Clinical Diabetes and Healthcare}
}

Introduction: The gut microbiota influences and interacts with the host metabolism through effects on nutrient metabolism and digestion. Duodenal Mucosal Resurfacing (DMR) is a novel endoscopic procedure involving duodenal mucosal ablation by the use of hydrothermal energy. DMR, when combined with a glucagon-like peptide-1 receptor agonist (GLP-1RA), resulted in discontinuation of exogenous insulin treatment in 69% of patients with insulin dependent type 2 diabetes mellitus (T2DM) in the INSPIRE study. These patients also experienced improved glycaemic control and metabolic health. We thus investigated if these clinical effects were associated with a change in gut microbiota alpha and beta diversity. Methods: Faecal samples from the 16 patients were obtained for Illumina shotgun sequencing at baseline and 3 months after DMR. We assessed alpha and beta diversity of the gut microbiota in these samples and analysed its correlations with changes in HbA1c, body weight, and liver MRI proton density fat fraction (PDFF). Results: HbA1c correlated negatively with alpha diversity (p=0.011, rho: -0.62) whereas changes in PDFF correlated significantly with beta diversity (p=0.036, rho: 0.55) 3 months after initiation of the combined intervention. These correlations with metabolic parameters were observed despite finding no change in gut microbiota diversity at 3 months post DMR. Discussion: The correlation between gut microbiota richness (alpha diversity) and HbA1c as well as the change in PDFF and changed microbiota composition (beta diversity) suggests that changed gut microbiota diversity is associated with metabolic improvements after DMR in combination with glucagon-like-peptide-1 receptor agonist in type 2 diabetes. Larger controlled studies are however needed to find causal links between DMR with GLP-1RA, the gut microbiota, and improvements in metabolic health.

@article{
 title = {Human milk oligosaccharides alleviate stress-induced visceral hypersensitivity and associated microbiota dysbiosis},
 type = {article},
 year = {2022},
 keywords = {HMOs,abdominal pain,antibiotics,chronic psychological stress,metagenomic,microbiome},
 volume = {99},
 month = {1},
 publisher = {Elsevier Inc.},
 day = {1},
 id = {a27968f3-9860-3e5c-95ef-cf67630b65ee},
 created = {2025-10-30T12:05:03.064Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:07.182Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Pain-related functional gastrointestinal disorders (FGIDs) are characterized by visceral hypersensitivity (VHS) associated with alterations in the microbiota-gut-brain axis. Since human milk oligosaccharides (HMOs) modulate microbiota, gut and brain, we investigated whether HMOs impact VHS, and explored the role of gut microbiota. To induce VHS, C57BL/6JRj mice received hourly water avoidance stress (WAS) sessions for 10 d, or antibiotics (ATB) for 12 d. Challenged and unchallenged (Sham) animals were fed AIN93M diet (Cont) or AIN93M containing 1% of a 6-HMO mix (HMO6). VHS was assessed by monitoring the visceromotor response to colorectal distension. Fecal microbiome was analyzed by shotgun metagenomics. The effect of HMO6 sub-blends on VHS and nociceptive pathways was further tested using the WAS model. In mice fed Cont, WAS and ATB increased the visceromotor response to distension. HMO6 decreased WAS-mediated electromyographic rise at most distension volumes and overall Area Under Curve (AUC=6.12±0.50 in WAS/HMO6 vs. 9.46±0.50 in WAS/Cont; P<.0001). In contrast, VHS in ATB animals was not improved by HMO6. In WAS, HMO6 promoted most microbiota taxa and several functional pathways associated with low VHS and decreased those associated with high VHS. Among the sub-blends, 2’FL+DFL and LNT+6’SL reduced visceromotor response close to Sham/Cont values and modulated serotoninergic and CGRPα-related pathways. This research further substantiates the capacity of HMOs to modulate the microbiota-gut-brain communication and identifies mitigation of abdominal pain as a new HMO benefit. Ultimately, our findings suggest the value of specific HMO blends to alleviate pain associated FGIDs such as infantile colic or Irritable Bowel Syndrome.},
 bibtype = {article},
 author = {Ferrier, Laurent and Eutamène, Hélène and Siegwald, Léa and Marquard, Andrea M. and Tondereau, Valerie and Chevalier, Julien and Jacot, Guillaume E. and Favre, Laurent and Theodorou, Vassilia and Vicario, Maria and Rytz, Andreas and Bergonzelli, Gabriela and Garcia-Rodenas, Clara L.},
 doi = {10.1016/J.JNUTBIO.2021.108865},
 journal = {Journal of Nutritional Biochemistry}
}

Pain-related functional gastrointestinal disorders (FGIDs) are characterized by visceral hypersensitivity (VHS) associated with alterations in the microbiota-gut-brain axis. Since human milk oligosaccharides (HMOs) modulate microbiota, gut and brain, we investigated whether HMOs impact VHS, and explored the role of gut microbiota. To induce VHS, C57BL/6JRj mice received hourly water avoidance stress (WAS) sessions for 10 d, or antibiotics (ATB) for 12 d. Challenged and unchallenged (Sham) animals were fed AIN93M diet (Cont) or AIN93M containing 1% of a 6-HMO mix (HMO6). VHS was assessed by monitoring the visceromotor response to colorectal distension. Fecal microbiome was analyzed by shotgun metagenomics. The effect of HMO6 sub-blends on VHS and nociceptive pathways was further tested using the WAS model. In mice fed Cont, WAS and ATB increased the visceromotor response to distension. HMO6 decreased WAS-mediated electromyographic rise at most distension volumes and overall Area Under Curve (AUC=6.12±0.50 in WAS/HMO6 vs. 9.46±0.50 in WAS/Cont; P<.0001). In contrast, VHS in ATB animals was not improved by HMO6. In WAS, HMO6 promoted most microbiota taxa and several functional pathways associated with low VHS and decreased those associated with high VHS. Among the sub-blends, 2’FL+DFL and LNT+6’SL reduced visceromotor response close to Sham/Cont values and modulated serotoninergic and CGRPα-related pathways. This research further substantiates the capacity of HMOs to modulate the microbiota-gut-brain communication and identifies mitigation of abdominal pain as a new HMO benefit. Ultimately, our findings suggest the value of specific HMO blends to alleviate pain associated FGIDs such as infantile colic or Irritable Bowel Syndrome.

@article{
 title = {Multiomics signatures of type 1 diabetes with and without albuminuria},
 type = {article},
 year = {2022},
 keywords = {albuminuria,lipidomics,metabolomics,microbiome,multiomics,phageome,type 1 diabetes},
 volume = {13},
 month = {12},
 publisher = {Frontiers Media S.A.},
 day = {2},
 id = {6bb4221a-6ce8-39d9-8a17-f09e93c51750},
 created = {2025-10-30T12:05:03.115Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:12.196Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Aims/hypothesis: To identify novel pathophysiological signatures of longstanding type 1 diabetes (T1D) with and without albuminuria we investigated the gut microbiome and blood metabolome in individuals with T1D and healthy controls (HC). We also mapped the functional underpinnings of the microbiome in relation to its metabolic role. Methods: One hundred and sixty-one individuals with T1D and 50 HC were recruited at the Steno Diabetes Center Copenhagen, Denmark. T1D cases were stratified based on levels of albuminuria into normoalbuminuria, moderate and severely increased albuminuria. Shotgun sequencing of bacterial and viral microbiome in stool samples and circulating metabolites and lipids profiling using mass spectroscopy in plasma of all participants were performed. Functional mapping of microbiome into Gut Metabolic Modules (GMMs) was done using EggNog and KEGG databases. Multiomics integration was performed using MOFA tool. Results: Measures of the gut bacterial beta diversity differed significantly between T1D and HC, either with moderately or severely increased albuminuria. Taxonomic analyses of the bacterial microbiota identified 51 species that differed in absolute abundance between T1D and HC (17 higher, 34 lower). Stratified on levels of albuminuria, 10 species were differentially abundant for the moderately increased albuminuria group, 63 for the severely increased albuminuria group while 25 were common and differentially abundant both for moderately and severely increased albuminuria groups, when compared to HC. Functional characterization of the bacteriome identified 23 differentially enriched GMMs between T1D and HC, mostly involved in sugar and amino acid metabolism. No differences in relation to albuminuria stratification was observed. Twenty-five phages were differentially abundant between T1D and HC groups. Six of these varied with albuminuria status. Plasma metabolomics indicated differences in the steroidogenesis and sugar metabolism and circulating sphingolipids in T1D individuals. We identified association between sphingolipid levels and Bacteroides sp. abundances. MOFA revealed reduced interactions between gut microbiome and plasma metabolome profiles albeit polar metabolite, lipids and bacteriome compositions contributed to the variance in albuminuria levels among T1D individuals. Conclusions: Individuals with T1D and progressive kidney disease stratified on levels of albuminuria show distinct signatures in their gut microbiome and blood metabolome.},
 bibtype = {article},
 author = {Clos-Garcia, Marc and Ahluwalia, Tarunveer S. and Winther, Signe A. and Henriksen, Peter and Ali, Mina and Fan, Yong and Stankevic, Evelina and Lyu, Liwei and Vogt, Josef K. and Hansen, Torben and Legido-Quigley, Cristina and Rossing, Peter and Pedersen, Oluf},
 doi = {10.3389/FENDO.2022.1015557},
 journal = {Frontiers in Endocrinology}
}

Aims/hypothesis: To identify novel pathophysiological signatures of longstanding type 1 diabetes (T1D) with and without albuminuria we investigated the gut microbiome and blood metabolome in individuals with T1D and healthy controls (HC). We also mapped the functional underpinnings of the microbiome in relation to its metabolic role. Methods: One hundred and sixty-one individuals with T1D and 50 HC were recruited at the Steno Diabetes Center Copenhagen, Denmark. T1D cases were stratified based on levels of albuminuria into normoalbuminuria, moderate and severely increased albuminuria. Shotgun sequencing of bacterial and viral microbiome in stool samples and circulating metabolites and lipids profiling using mass spectroscopy in plasma of all participants were performed. Functional mapping of microbiome into Gut Metabolic Modules (GMMs) was done using EggNog and KEGG databases. Multiomics integration was performed using MOFA tool. Results: Measures of the gut bacterial beta diversity differed significantly between T1D and HC, either with moderately or severely increased albuminuria. Taxonomic analyses of the bacterial microbiota identified 51 species that differed in absolute abundance between T1D and HC (17 higher, 34 lower). Stratified on levels of albuminuria, 10 species were differentially abundant for the moderately increased albuminuria group, 63 for the severely increased albuminuria group while 25 were common and differentially abundant both for moderately and severely increased albuminuria groups, when compared to HC. Functional characterization of the bacteriome identified 23 differentially enriched GMMs between T1D and HC, mostly involved in sugar and amino acid metabolism. No differences in relation to albuminuria stratification was observed. Twenty-five phages were differentially abundant between T1D and HC groups. Six of these varied with albuminuria status. Plasma metabolomics indicated differences in the steroidogenesis and sugar metabolism and circulating sphingolipids in T1D individuals. We identified association between sphingolipid levels and Bacteroides sp. abundances. MOFA revealed reduced interactions between gut microbiome and plasma metabolome profiles albeit polar metabolite, lipids and bacteriome compositions contributed to the variance in albuminuria levels among T1D individuals. Conclusions: Individuals with T1D and progressive kidney disease stratified on levels of albuminuria show distinct signatures in their gut microbiome and blood metabolome.

@article{
 title = { Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double‐blind, placebo‐controlled Phase 2 trial },
 type = {article},
 year = {2022},
 volume = {12},
 month = {5},
 publisher = {Wiley},
 id = {ae4360e8-f6cf-3f89-8f35-e9dae0f5b168},
 created = {2025-10-30T12:05:03.185Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.185Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {BACKGROUND In patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed. METHODS AND FINDINGS In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double-blind and placebo-controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild-to-severe AD (EudraCT:2016-003501-33). ATx201 has a narrow minimal inhibitory concentration distribution (.125-.5 μg/ml) consistent with its mode of action - targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin-resistant S. aureus. In a Phase 2 trial in patients with mild-to-severe AD (N = 36), twice-daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle. CONCLUSION These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.},
 bibtype = {article},
 author = {Weiss, Anne and Delavenne, Emilie and Matias, Carina and Lagler, Heimo and Simon, Daniel and Li, Ping and Hansen, Jon U. and dos Santos, Teresa Pires and Jana, Bimal and Priemel, Petra and Bangert, Christine and Bauer, Martin and Eberl, Sabine and Nussbaumer‐Pröll, Alina and Anne Österreicher, Zoe and Matzneller, Peter and Quint, Tamara and Weber, Maria and Nielsen, Hanne Mørck and Rades, Thomas and Johansen, Helle Krogh and Westh, Henrik and Kim, Wooseong and Mylonakis, Eleftherios and Friis, Christian and Guardabassi, Luca and Pace, John and Lundberg, Carina Vingsbo and M'Zali, Fatima and Butty, Pascal and Sørensen, Nikolaj and Nielsen, Henrik Bjørn and Toft‐Kehler, Rasmus and Guttman‐Yassky, Emma and Stingl, Georg and Zeitlinger, Markus and Sommer, Morten},
 doi = {10.1002/CTM2.790},
 journal = {Clinical and Translational Medicine},
 number = {5}
}

BACKGROUND In patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed. METHODS AND FINDINGS In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double-blind and placebo-controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild-to-severe AD (EudraCT:2016-003501-33). ATx201 has a narrow minimal inhibitory concentration distribution (.125-.5 μg/ml) consistent with its mode of action - targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin-resistant S. aureus. In a Phase 2 trial in patients with mild-to-severe AD (N = 36), twice-daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle. CONCLUSION These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.

@article{
 title = {Oxford Nanopore R10.4 long-read sequencing enables the generation of near-finished bacterial genomes from pure cultures and metagenomes without short-read or reference polishing},
 type = {article},
 year = {2022},
 pages = {823-826},
 volume = {19},
 month = {7},
 publisher = {Nature Research},
 day = {1},
 id = {f4c7bcf5-dec9-3c1f-8c29-a42c3a086b95},
 created = {2025-10-30T12:18:14.020Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:18:17.418Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Long-read Oxford Nanopore sequencing has democratized microbial genome sequencing and enables the recovery of highly contiguous microbial genomes from isolates or metagenomes. However, to obtain near-finished genomes it has been necessary to include short-read polishing to correct insertions and deletions derived from homopolymer regions. Here, we show that Oxford Nanopore R10.4 can be used to generate near-finished microbial genomes from isolates or metagenomes without short-read or reference polishing.},
 bibtype = {article},
 author = {Sereika, Mantas and Kirkegaard, Rasmus Hansen and Karst, Søren Michael and Michaelsen, Thomas Yssing and Sørensen, Emil Aarre and Wollenberg, Rasmus Dam and Albertsen, Mads},
 doi = {10.1038/s41592-022-01539-7},
 journal = {Nature Methods},
 number = {7}
}

Long-read Oxford Nanopore sequencing has democratized microbial genome sequencing and enables the recovery of highly contiguous microbial genomes from isolates or metagenomes. However, to obtain near-finished genomes it has been necessary to include short-read polishing to correct insertions and deletions derived from homopolymer regions. Here, we show that Oxford Nanopore R10.4 can be used to generate near-finished microbial genomes from isolates or metagenomes without short-read or reference polishing.

@article{
 title = {Gut microbial dysbiosis correlates with stroke severity markers in aged rats.},
 type = {article},
 year = {2022},
 keywords = {aging,imaging,inflammation,microbiome,stroke},
 volume = {1},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/36825211,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9945937},
 publisher = {Frontiers Media SA},
 id = {f6c2b1ef-d20c-311c-ad25-abd47899b069},
 created = {2025-10-30T12:26:00.878Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.878Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {BACKGROUND An imbalanced gut microbial community, or dysbiosis, has been shown to occur following stroke. It is possible that this dysbiosis negatively impacts stroke recovery and rehabilitation. Species level resolution measurements of the gut microbiome following stroke are needed to develop and test precision interventions such as probiotic or fecal microbiota transplant therapies that target the gut microbiome. Previous studies have used 16S rRNA amplicon sequencing in young male mice to obtain broad profiling of the gut microbiome at the genus level following stroke, but further investigations will be needed with whole genome shotgun sequencing in aged rats of both sexes to obtain species level resolution in a model which will better translate to the demographics of human stroke patients. METHODS Thirty-nine aged male and female rats underwent middle cerebral artery occlusion. Fecal samples were collected before stroke and 3 days post stroke to measure gut microbiome. Machine learning was used to identify the top ranked bacteria which were changed following stroke. MRI imaging was used to obtain infarct and edema size and cerebral blood flow (CBF). ELISA was used to obtain inflammatory markers. RESULTS Dysbiosis was demonstrated by an increase in pathogenic bacteria such as Butyricimonas virosa (15.52 fold change, p < 0.0001), Bacteroides vulgatus (7.36 fold change, p < 0.0001), and Escherichia coli (47.67 fold change, p < 0.0001). These bacteria were positively associated with infarct and edema size and with the inflammatory markers Ccl19, Ccl24, IL17a, IL3, and complement C5; they were negatively correlated with CBF. Conversely, beneficial bacteria such as Ruminococcus flavefaciens (0.14 fold change, p < 0.0001), Akkermansia muciniphila (0.78 fold change, p < 0.0001), and Lactobacillus murinus (0.40 fold change, p < 0.0001) were decreased following stroke and associated with all the previous parameters in the opposite direction of the pathogenic species. There were not significant microbiome differences between the sexes. CONCLUSION The species level resolution measurements found here can be used as a foundation to develop and test precision interventions targeting the gut microbiome following stroke. Probiotics that include Ruminococcus flavefaciens, Akkermansia muciniphila, and Lactobacillus murinus should be developed to target the deficit following stroke to measure the impact on stroke severity.},
 bibtype = {article},
 author = {Hammond, Tyler C and Messmer, Sarah and Frank, Jacqueline A and Lukins, Doug and Colwell, Rita and Lin, Ai-Ling and Pennypacker, Keith R},
 doi = {10.3389/fstro.2022.1026066},
 journal = {Frontiers in stroke}
}

BACKGROUND An imbalanced gut microbial community, or dysbiosis, has been shown to occur following stroke. It is possible that this dysbiosis negatively impacts stroke recovery and rehabilitation. Species level resolution measurements of the gut microbiome following stroke are needed to develop and test precision interventions such as probiotic or fecal microbiota transplant therapies that target the gut microbiome. Previous studies have used 16S rRNA amplicon sequencing in young male mice to obtain broad profiling of the gut microbiome at the genus level following stroke, but further investigations will be needed with whole genome shotgun sequencing in aged rats of both sexes to obtain species level resolution in a model which will better translate to the demographics of human stroke patients. METHODS Thirty-nine aged male and female rats underwent middle cerebral artery occlusion. Fecal samples were collected before stroke and 3 days post stroke to measure gut microbiome. Machine learning was used to identify the top ranked bacteria which were changed following stroke. MRI imaging was used to obtain infarct and edema size and cerebral blood flow (CBF). ELISA was used to obtain inflammatory markers. RESULTS Dysbiosis was demonstrated by an increase in pathogenic bacteria such as Butyricimonas virosa (15.52 fold change, p < 0.0001), Bacteroides vulgatus (7.36 fold change, p < 0.0001), and Escherichia coli (47.67 fold change, p < 0.0001). These bacteria were positively associated with infarct and edema size and with the inflammatory markers Ccl19, Ccl24, IL17a, IL3, and complement C5; they were negatively correlated with CBF. Conversely, beneficial bacteria such as Ruminococcus flavefaciens (0.14 fold change, p < 0.0001), Akkermansia muciniphila (0.78 fold change, p < 0.0001), and Lactobacillus murinus (0.40 fold change, p < 0.0001) were decreased following stroke and associated with all the previous parameters in the opposite direction of the pathogenic species. There were not significant microbiome differences between the sexes. CONCLUSION The species level resolution measurements found here can be used as a foundation to develop and test precision interventions targeting the gut microbiome following stroke. Probiotics that include Ruminococcus flavefaciens, Akkermansia muciniphila, and Lactobacillus murinus should be developed to target the deficit following stroke to measure the impact on stroke severity.

@article{
 title = {Fungal Dysbiosis in Children with Celiac Disease},
 type = {article},
 year = {2022},
 keywords = {Celiac disease,Dysbiosis,Fungi,Microbiota,Saudi children},
 pages = {216-223},
 volume = {67},
 month = {1},
 publisher = {Springer},
 day = {1},
 id = {78076da2-2e37-39aa-b8da-17ae6d9e58a8},
 created = {2025-10-30T12:26:00.984Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.984Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Although intestinal fungi are known to interact with the immune system, the relationship between intestinal fungi and childhood celiac disease (CeD), an immune-mediated condition, has rarely been reported. Aims: The aim of this study was to describe gut fungal profiles in a cohort of children with new-onset CeD. Methods: Mucosal and fecal samples were collected from children with CeD and controls and subjected to metagenomics analysis of fungal microbiota communities. DNA libraries were sequenced using Illumina HiSeq platform 2 × 150 bp. Bioinformatic analysis was performed to quantify the relative abundance of fungi. Shannon alpha diversity metrics and beta diversity principal coordinate (PCo) analyses were calculated, and DESeq tests were performed between celiac and non-celiac groups. Results: Overall more abundant taxa in samples of children with CeD included Tricholomataceae, Saccharomycetaceae, Saccharomycetes Saccharomyces cerevisiae, and Candida, whereas less abundant taxa included Pichiaceae, Pichia kudriavzevii, Pneumocystis, and Pneumocystis jirovecii. Alpha diversity between CeD and control individuals did not differ significantly, and beta diversity PCo analysis showed overlap of samples from CeD and controls for both fecal or mucosal samples; however, there was a clear separation between mucosal and fecal overall samples Conclusions: We report fungal dysbiosis in children with CeD, suggesting a possible role in the pathogenesis of CeD. Further larger, controlled, prospective and longitudinal studies are needed to verify the results of this study and clarify the functional role of fungi in CeD.},
 bibtype = {article},
 author = {El Mouzan, Mohammad and Al-Hussaini, Abdulrahman and Fanelli, Brian and Assiri, Asaad and AlSaleem, Badr and Al Mofarreh, Mohammad and Al Sarkhy, Ahmed and Alasmi, Mona},
 doi = {10.1007/S10620-021-06823-8},
 journal = {Digestive Diseases and Sciences},
 number = {1}
}

Background: Although intestinal fungi are known to interact with the immune system, the relationship between intestinal fungi and childhood celiac disease (CeD), an immune-mediated condition, has rarely been reported. Aims: The aim of this study was to describe gut fungal profiles in a cohort of children with new-onset CeD. Methods: Mucosal and fecal samples were collected from children with CeD and controls and subjected to metagenomics analysis of fungal microbiota communities. DNA libraries were sequenced using Illumina HiSeq platform 2 × 150 bp. Bioinformatic analysis was performed to quantify the relative abundance of fungi. Shannon alpha diversity metrics and beta diversity principal coordinate (PCo) analyses were calculated, and DESeq tests were performed between celiac and non-celiac groups. Results: Overall more abundant taxa in samples of children with CeD included Tricholomataceae, Saccharomycetaceae, Saccharomycetes Saccharomyces cerevisiae, and Candida, whereas less abundant taxa included Pichiaceae, Pichia kudriavzevii, Pneumocystis, and Pneumocystis jirovecii. Alpha diversity between CeD and control individuals did not differ significantly, and beta diversity PCo analysis showed overlap of samples from CeD and controls for both fecal or mucosal samples; however, there was a clear separation between mucosal and fecal overall samples Conclusions: We report fungal dysbiosis in children with CeD, suggesting a possible role in the pathogenesis of CeD. Further larger, controlled, prospective and longitudinal studies are needed to verify the results of this study and clarify the functional role of fungi in CeD.

@article{
 title = {The Neuro-Endo-Microbio-Ome Study: A Pilot Study of Neurobiological Alterations Pre- Versus Post-Bariatric Surgery},
 type = {article},
 year = {2022},
 keywords = {Roux-en-Y gastric bypass,bariatric surgery,cognition,gut hormones,gut microbiome,obesity,resting state functional magnetic resonance imaging,vertical sleeve gastrectomy},
 pages = {362-378},
 volume = {24},
 month = {7},
 publisher = {SAGE Publications Inc.},
 day = {1},
 id = {17f8b289-578a-3ff8-a74b-9ecd16b32f77},
 created = {2025-10-30T12:26:00.990Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.990Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Plausible phenotype mechanisms following bariatric surgery include changes in neural and gastrointestinal physiology. This pilot study aims to investigate individual and combined neurologic, gut microbiome, and plasma hormone changes pre- versus post-vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), and medical weight loss (MWL). We hypothesized post-weight loss phenotype would be associated with changes in central reward system brain connectivity, differences in postprandial gut hormone responses, and increased gut microbiome diversity. Methods: Subjects included participants undergoing VSG, n = 7; RYGB, n = 9; and MWL, n = 6. Ghrelin, glucagon-like peptide-1, peptide-YY, gut microbiome, and resting state functional magnetic resonance imaging (rsfMRI; using fractional amplitude of low-frequency fluctuations [fALFF]) were measured pre- and post-intervention in fasting and fed states. We explored phenotype characterization using clustering on gut hormone, microbiome, and rsfMRI datasets and a combined analysis. Results: We observed more widespread fALFF differences post-bariatric surgery versus post-MWL. Decreased post-prandial fALFF was seen in food reward regions post-RYGB. The highest number of microbial taxa that increased post-intervention occurred in the RYGB group, followed by VSG and MWL. The combined hormone, microbiome, and MRI dataset most accurately clustered samples into pre- versus post-VSG phenotypes followed by RYGB subjects. Conclusion: The data suggest surgical weight loss (VSG and RYGB) has a bigger impact on brain and gut function versus MWL and leads to lesser post-prandial activation of food-related neural circuits. VSG subjects had the greatest phenotype differences in interactions of microbiome, rsfMRI, and gut hormone features, followed by RYGB and MWL. These results will inform future prospective research studying gut-brain changes post-bariatric surgery.},
 bibtype = {article},
 author = {Agarwal, Khushbu and Maki, Katherine A. and Vizioli, Carlotta and Carnell, Susan and Goodman, Ethan and Hurley, Matthew and Harris, Civonnia and Colwell, Rita and Steele, Kimberley and Joseph, Paule V.},
 doi = {10.1177/10998004221085976},
 journal = {Biological Research for Nursing},
 number = {3}
}

Background: Plausible phenotype mechanisms following bariatric surgery include changes in neural and gastrointestinal physiology. This pilot study aims to investigate individual and combined neurologic, gut microbiome, and plasma hormone changes pre- versus post-vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), and medical weight loss (MWL). We hypothesized post-weight loss phenotype would be associated with changes in central reward system brain connectivity, differences in postprandial gut hormone responses, and increased gut microbiome diversity. Methods: Subjects included participants undergoing VSG, n = 7; RYGB, n = 9; and MWL, n = 6. Ghrelin, glucagon-like peptide-1, peptide-YY, gut microbiome, and resting state functional magnetic resonance imaging (rsfMRI; using fractional amplitude of low-frequency fluctuations [fALFF]) were measured pre- and post-intervention in fasting and fed states. We explored phenotype characterization using clustering on gut hormone, microbiome, and rsfMRI datasets and a combined analysis. Results: We observed more widespread fALFF differences post-bariatric surgery versus post-MWL. Decreased post-prandial fALFF was seen in food reward regions post-RYGB. The highest number of microbial taxa that increased post-intervention occurred in the RYGB group, followed by VSG and MWL. The combined hormone, microbiome, and MRI dataset most accurately clustered samples into pre- versus post-VSG phenotypes followed by RYGB subjects. Conclusion: The data suggest surgical weight loss (VSG and RYGB) has a bigger impact on brain and gut function versus MWL and leads to lesser post-prandial activation of food-related neural circuits. VSG subjects had the greatest phenotype differences in interactions of microbiome, rsfMRI, and gut hormone features, followed by RYGB and MWL. These results will inform future prospective research studying gut-brain changes post-bariatric surgery.

@article{
 title = {Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase.},
 type = {article},
 year = {2022},
 keywords = {Cerebral blood flow,Inulin diet,MRI,Machine learning,Short chain fatty acids,Traumatic brain injury,gut microbiome},
 pages = {50-64},
 volume = {4},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/35611116,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9126115},
 month = {4},
 publisher = {Scientific Archives LLC},
 day = {30},
 id = {63ba752b-a814-3a1c-877f-c05ccea55e99},
 created = {2025-10-30T12:26:01.022Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.022Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Mild traumatic brain injury (mTBI) has been shown to acutely alter the gut microbiome diversity and composition, known as dysbiosis, which can further exacerbate metabolic and vascular changes in the brain in both humans and rodents. However, it remains unknown how mTBI affects the gut microbiome in the chronic phase recovery (past one week post injury). It is also unknown if injury recovery can be improved by mitigating dysbiosis. The goal of the study is to fill the knowledge gap. First, we aim to understand how mTBI alters the gut microbiome through the chronic period of recovery (3 months post injury). In addition, as the gut microbiome can be modulated by diet, we also investigated if prebiotic inulin, a fermentable fiber that promotes growth of beneficial bacteria and metabolites, would mitigate dysbiosis, improve systemic metabolism, and protect brain structural and vascular integrity when administered after 3 months post closed head injury (CHI). We found that CHI given to male mice at 4 months of age induced gut dysbiosis which peaked at 1.5 months post injury, reduced cerebral blood flow (CBF) and altered brain white matter integrity. Interestingly, we also found that Sham mice had transient dysbiosis, which peaked 24 hours after injury and then normalized. After 8 weeks of inulin feeding, CHI mice had increased abundance of beneficial/anti-inflammatory bacteria, reduced abundance of pathogenic bacteria, enriched levels of short-chain fatty acids, and restored CBF in both hippocampi and left thalamus, compared to the CHI-control fed and Sham groups. Using machine learning, we further identified top bacterial species that separate Sham and CHI mice with and without the diet. Our results indicate that there is an injury- and time-dependent dysbiosis between CHI and Sham mice; inulin is effective to mitigate dysbiosis and improve brain injury recovery in the CHI mice. As there are currently no effective treatments for mTBI, the study may have profound implications for developing therapeutics or preventive interventions in the future.},
 bibtype = {article},
 author = {Yanckello, Lucille M and Fanelli, Brian and McCulloch, Scott and Xing, Xin and Sun, McKenna and Hammond, Tyler C and Colwell, Rita and Gu, Zezong and Ericsson, Aaron C and Chang, Ya-Hsuan and Bachstetter, Adam D and Lin, Ai-Ling},
 doi = {10.33696/immunology.4.132},
 journal = {Journal of cellular immunology},
 number = {2}
}

Mild traumatic brain injury (mTBI) has been shown to acutely alter the gut microbiome diversity and composition, known as dysbiosis, which can further exacerbate metabolic and vascular changes in the brain in both humans and rodents. However, it remains unknown how mTBI affects the gut microbiome in the chronic phase recovery (past one week post injury). It is also unknown if injury recovery can be improved by mitigating dysbiosis. The goal of the study is to fill the knowledge gap. First, we aim to understand how mTBI alters the gut microbiome through the chronic period of recovery (3 months post injury). In addition, as the gut microbiome can be modulated by diet, we also investigated if prebiotic inulin, a fermentable fiber that promotes growth of beneficial bacteria and metabolites, would mitigate dysbiosis, improve systemic metabolism, and protect brain structural and vascular integrity when administered after 3 months post closed head injury (CHI). We found that CHI given to male mice at 4 months of age induced gut dysbiosis which peaked at 1.5 months post injury, reduced cerebral blood flow (CBF) and altered brain white matter integrity. Interestingly, we also found that Sham mice had transient dysbiosis, which peaked 24 hours after injury and then normalized. After 8 weeks of inulin feeding, CHI mice had increased abundance of beneficial/anti-inflammatory bacteria, reduced abundance of pathogenic bacteria, enriched levels of short-chain fatty acids, and restored CBF in both hippocampi and left thalamus, compared to the CHI-control fed and Sham groups. Using machine learning, we further identified top bacterial species that separate Sham and CHI mice with and without the diet. Our results indicate that there is an injury- and time-dependent dysbiosis between CHI and Sham mice; inulin is effective to mitigate dysbiosis and improve brain injury recovery in the CHI mice. As there are currently no effective treatments for mTBI, the study may have profound implications for developing therapeutics or preventive interventions in the future.

@article{
 title = {Metagenomics of diabetic foot ulcer undergoing treatment with total contact casting: A case study},
 type = {article},
 year = {2022},
 pages = {S45-S49},
 volume = {31},
 month = {9},
 publisher = {MA Healthcare Ltd},
 day = {1},
 id = {872fa8d8-400b-37d4-bf56-d93042045ead},
 created = {2025-10-30T12:26:01.035Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.035Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Objective: Diabetic foot ulcers (DFUs) are characterised by the presence of many microbes, some of which may not be identified by traditional culture techniques. Total contact casting (TCC) remains the gold-standard for offloading, yet little is known about the microbiome of wounds that progress from hard-to-heal to closed within a TCC. Method: A patient with a DFU underwent weekly treatment with TCC to closure. Samples for next-generation sequencing (NGS) and bioinformatics analysis of tissue samples were collected during each visit. Detection, identification, characterisation of the microbial community and abundance of microbes in each sample were compared. Results: Abundance of microbes, identified by species and strain, changed with each treatment visit. By the final week of treatment, species diversity of the wound microbiome had decreased significantly, highlighted by an observed decrease in the number of total microorganisms present. Resistance genes for tetracyclines were detected in the first sample, but not in subsequent samples. Conclusion: The results of this study suggest dynamic microbiological changes associated with DFUs as they progress to healing within a TCC. As NGS becomes more readily available, further studies will be helpful to gain an improved understanding of the significance of the wound microbiome in patients with?DFUs.},
 bibtype = {article},
 author = {Isaac, Adam L. and Tritto, Michael and Colwell, Rita R. and Armstrong, David G.},
 doi = {10.12968/jowc.2022.31.Sup9.S45},
 journal = {Journal of Wound Care}
}

Objective: Diabetic foot ulcers (DFUs) are characterised by the presence of many microbes, some of which may not be identified by traditional culture techniques. Total contact casting (TCC) remains the gold-standard for offloading, yet little is known about the microbiome of wounds that progress from hard-to-heal to closed within a TCC. Method: A patient with a DFU underwent weekly treatment with TCC to closure. Samples for next-generation sequencing (NGS) and bioinformatics analysis of tissue samples were collected during each visit. Detection, identification, characterisation of the microbial community and abundance of microbes in each sample were compared. Results: Abundance of microbes, identified by species and strain, changed with each treatment visit. By the final week of treatment, species diversity of the wound microbiome had decreased significantly, highlighted by an observed decrease in the number of total microorganisms present. Resistance genes for tetracyclines were detected in the first sample, but not in subsequent samples. Conclusion: The results of this study suggest dynamic microbiological changes associated with DFUs as they progress to healing within a TCC. As NGS becomes more readily available, further studies will be helpful to gain an improved understanding of the significance of the wound microbiome in patients with?DFUs.

@article{
 title = {Analysis of the Ability of Capsaicin to Modulate the Human Gut Microbiota In Vitro},
 type = {article},
 year = {2022},
 keywords = {Capsaicin,Gut microbiota,Short-chain fatty acids (SCFAs),Untargeted metabolomics},
 volume = {14},
 month = {3},
 publisher = {MDPI},
 day = {1},
 id = {113d4910-7666-344d-8745-37aabc1fa8f6},
 created = {2025-10-30T12:26:01.256Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:11.461Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Previous studies on capsaicin, the bioactive compound in chili peppers, have shown that it may have a beneficial effect in vivo when part of a regular diet. These positive health benefits, including an anti-inflammatory potential and protective effects against obesity, are often attributed to the gut microbial community response to capsaicin. However, there is no consensus on the mechanism behind the protective effect of capsaicin. In this study, we used an in vitro model of the human gut microbiota to determine how regular consumption of capsaicin impacts the gut microbiota. Using a combination of NextGen sequencing and metabolomics, we found that regular capsaicin treatment changed the structure of the gut microbial community by increasing diversity and certain SCFA abundances, particularly butanoic acid. Through this study, we determined that the addition of capsaicin to the in vitro cultures of the human gut microbiome resulted in increased diversity of the microbial community and an increase in butanoic acid. These changes may be responsible for the health benefits associated with CAP consumption.},
 bibtype = {article},
 author = {Mahalak, Karley K. and Bobokalonov, Jamshed and Firrman, Jenni and Williams, Russell and Evans, Bradley and Fanelli, Brian and Soares, Jason W. and Kobori, Masuko and Liu, Linshu},
 doi = {10.3390/nu14061283},
 journal = {Nutrients},
 number = {6}
}

Previous studies on capsaicin, the bioactive compound in chili peppers, have shown that it may have a beneficial effect in vivo when part of a regular diet. These positive health benefits, including an anti-inflammatory potential and protective effects against obesity, are often attributed to the gut microbial community response to capsaicin. However, there is no consensus on the mechanism behind the protective effect of capsaicin. In this study, we used an in vitro model of the human gut microbiota to determine how regular consumption of capsaicin impacts the gut microbiota. Using a combination of NextGen sequencing and metabolomics, we found that regular capsaicin treatment changed the structure of the gut microbial community by increasing diversity and certain SCFA abundances, particularly butanoic acid. Through this study, we determined that the addition of capsaicin to the in vitro cultures of the human gut microbiome resulted in increased diversity of the microbial community and an increase in butanoic acid. These changes may be responsible for the health benefits associated with CAP consumption.

@article{
 title = {Microbiome Analysis for Wastewater Surveillance during COVID-19},
 type = {article},
 year = {2022},
 keywords = {COVID-19,DNA sequencing,RNA sequencing,RT-qPCR,SARS-CoV-2,environmental risk,metagenomics,metatranscriptomics,microbiome,risk assessment,shotgun sequencing,wastewater,wastewater monitoring,wastewater surveillance,wastewater-based epidemiology,whole metagenome sequencing},
 volume = {13},
 month = {8},
 publisher = {American Society for Microbiology},
 day = {1},
 id = {b9e1d014-9042-34d8-9e7f-b1758354e027},
 created = {2025-10-30T12:26:01.295Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.295Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Wastewater surveillance (WS), when coupled with advanced molecular
techniques, offers near real-time monitoring of community-wide transmission of SARS-CoV-2 and allows assessing and mitigating COVID-19 outbreaks, by evaluating the total microbial assemblage in a community. Composite wastewater samples (24 h) were collected weekly from a manhole between December 2020 and November 2021 in Maryland, USA. RT-qPCR results showed concentrations of SARS-CoV-2 RNA recovered from wastewater samples reflected incidence of COVID-19 cases. When a drastic increase in COVID-19 was detected in February 2021, samples were selected for microbiome analysis (DNA metagenomics, RNA metatranscriptomics, and targeted SARS-CoV-2 sequencing). Targeted SARS-CoV-2 sequencing allowed for detection of important genetic mutations, such as spike: K417N, D614G, P681H, T716I, S982A, and D1118H, commonly associated with increased cell entry and reinfection. Microbiome analysis (DNA and RNA) provided important insight with respect to human health-related factors, including detection of pathogens and their virulence/antibiotic resistance genes. Specific microbial species comprising the wastewater microbiome correlated with incidence of SARS-CoV-2 RNA, suggesting potential association with SARS-CoV-2 infection. Climatic conditions, namely, temperature, were related to incidence of COVID-19 and detection of SARS-CoV-2 in wastewater, having been monitored as part of an environmental risk score assessment carried out in this study. In summary, the wastewater microbiome provides useful public health information, and hence, a valuable tool to proactively detect and characterize pathogenic agents circulating in a community. In effect, metagenomics of wastewater can serve as an early warning system for communicable diseases, by providing a larger source of information for health departments and public officials. IMPORTANCE Traditionally, testing for COVID-19 is done by detecting SARS-CoV-2 in samples collected from nasal swabs and/or saliva. However, SARS-CoV-2 can also be detected in feces of infected individuals. Therefore, wastewater samples can be used to test all individuals of a community contributing to the sewage collection system, i.e., the infrastructure, such as gravity pipes, manholes, tanks, lift stations, control structures, and force mains, that collects used water from residential and commercial sources and conveys the flow to a wastewater treatment plant. Here, we profile community wastewater collected from a manhole, detect presence of SARS-CoV-2, identify genetic mutations of SARS-CoV-2, and perform COVID-19 risk score assessment of the study area. Using metagenomics analysis, we also detect other microorganisms (bacteria, fungi, protists, and viruses) present in the samples. Results show that by analyzing all microorganisms present in wastewater, pathogens circulating in a community can provide an early warning for contagious diseases.},
 bibtype = {article},
 author = {Brumfield, Kyle D. and Leddy, Menu and Usmani, Moiz and Cotruvo, Joseph A. and Tien, Ching Tzone and Dorsey, Suzanne and Graubics, Karlis and Fanelli, Brian and Zhou, Isaac and Registe, Nathaniel and Dadlani, Manoj and Wimalarante, Malinda and Jinasena, Dilini and Abayagunawardena, Rushan and Withanachchi, Chiran and Huq, Anwar and Jutla, Antarpreet and Colwell, Rita R.},
 doi = {10.1128/mbio.00591-22},
 journal = {mBio},
 number = {4}
}

Wastewater surveillance (WS), when coupled with advanced molecular techniques, offers near real-time monitoring of community-wide transmission of SARS-CoV-2 and allows assessing and mitigating COVID-19 outbreaks, by evaluating the total microbial assemblage in a community. Composite wastewater samples (24 h) were collected weekly from a manhole between December 2020 and November 2021 in Maryland, USA. RT-qPCR results showed concentrations of SARS-CoV-2 RNA recovered from wastewater samples reflected incidence of COVID-19 cases. When a drastic increase in COVID-19 was detected in February 2021, samples were selected for microbiome analysis (DNA metagenomics, RNA metatranscriptomics, and targeted SARS-CoV-2 sequencing). Targeted SARS-CoV-2 sequencing allowed for detection of important genetic mutations, such as spike: K417N, D614G, P681H, T716I, S982A, and D1118H, commonly associated with increased cell entry and reinfection. Microbiome analysis (DNA and RNA) provided important insight with respect to human health-related factors, including detection of pathogens and their virulence/antibiotic resistance genes. Specific microbial species comprising the wastewater microbiome correlated with incidence of SARS-CoV-2 RNA, suggesting potential association with SARS-CoV-2 infection. Climatic conditions, namely, temperature, were related to incidence of COVID-19 and detection of SARS-CoV-2 in wastewater, having been monitored as part of an environmental risk score assessment carried out in this study. In summary, the wastewater microbiome provides useful public health information, and hence, a valuable tool to proactively detect and characterize pathogenic agents circulating in a community. In effect, metagenomics of wastewater can serve as an early warning system for communicable diseases, by providing a larger source of information for health departments and public officials. IMPORTANCE Traditionally, testing for COVID-19 is done by detecting SARS-CoV-2 in samples collected from nasal swabs and/or saliva. However, SARS-CoV-2 can also be detected in feces of infected individuals. Therefore, wastewater samples can be used to test all individuals of a community contributing to the sewage collection system, i.e., the infrastructure, such as gravity pipes, manholes, tanks, lift stations, control structures, and force mains, that collects used water from residential and commercial sources and conveys the flow to a wastewater treatment plant. Here, we profile community wastewater collected from a manhole, detect presence of SARS-CoV-2, identify genetic mutations of SARS-CoV-2, and perform COVID-19 risk score assessment of the study area. Using metagenomics analysis, we also detect other microorganisms (bacteria, fungi, protists, and viruses) present in the samples. Results show that by analyzing all microorganisms present in wastewater, pathogens circulating in a community can provide an early warning for contagious diseases.

@article{
 title = {Prior exposure to microcystin alters host gut resistome and is associated with dysregulated immune homeostasis in translatable mouse models},
 type = {article},
 year = {2022},
 volume = {12},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {e4855aef-bbe9-32b4-99b1-9455cea9a75c},
 created = {2025-10-30T12:26:01.916Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.916Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {A strong association between exposure to the common harmful algal bloom toxin microcystin and the altered host gut microbiome has been shown. We tested the hypothesis that prior exposure to the cyanotoxin microcystin-LR may alter the host resistome. We show that the mice exposed to microcystin-LR had an altered microbiome signature that harbored antibiotic resistance genes. Host resistome genotypes such as mefA, msrD, mel, ant6, and tet40 increased in diversity and relative abundance following microcystin-LR exposure. Interestingly, the increased abundance of these genes was traced to resistance to common antibiotics such as tetracycline, macrolides, glycopeptide, and aminoglycosides, crucial for modern-day treatment of several diseases. Increased abundance of these genes was positively associated with increased expression of PD1, a T-cell homeostasis marker, and pleiotropic inflammatory cytokine IL-6 with a concomitant negative association with immunosurveillance markers IL-7 and TLR2. Microcystin-LR exposure also caused decreased TLR2, TLR4, and REG3G expressions, increased immunosenescence, and higher systemic levels of IL-6 in both wild-type and humanized mice. In conclusion, the results show a first-ever characterization of the host resistome following microcystin-LR exposure and its connection to host immune status and antimicrobial resistance that can be crucial to understand treatment options with antibiotics in microcystin-exposed subjects in clinical settings.},
 bibtype = {article},
 author = {Saha, Punnag and Bose, Dipro and Stebliankin, Vitalii and Cickovski, Trevor and Seth, Ratanesh K. and Porter, Dwayne E. and Brooks, Bryan W. and Mathee, Kalai and Narasimhan, Giri and Colwell, Rita and Scott, Geoff I. and Chatterjee, Saurabh},
 doi = {10.1038/s41598-022-15708-3},
 journal = {Scientific Reports},
 number = {1}
}

A strong association between exposure to the common harmful algal bloom toxin microcystin and the altered host gut microbiome has been shown. We tested the hypothesis that prior exposure to the cyanotoxin microcystin-LR may alter the host resistome. We show that the mice exposed to microcystin-LR had an altered microbiome signature that harbored antibiotic resistance genes. Host resistome genotypes such as mefA, msrD, mel, ant6, and tet40 increased in diversity and relative abundance following microcystin-LR exposure. Interestingly, the increased abundance of these genes was traced to resistance to common antibiotics such as tetracycline, macrolides, glycopeptide, and aminoglycosides, crucial for modern-day treatment of several diseases. Increased abundance of these genes was positively associated with increased expression of PD1, a T-cell homeostasis marker, and pleiotropic inflammatory cytokine IL-6 with a concomitant negative association with immunosurveillance markers IL-7 and TLR2. Microcystin-LR exposure also caused decreased TLR2, TLR4, and REG3G expressions, increased immunosenescence, and higher systemic levels of IL-6 in both wild-type and humanized mice. In conclusion, the results show a first-ever characterization of the host resistome following microcystin-LR exposure and its connection to host immune status and antimicrobial resistance that can be crucial to understand treatment options with antibiotics in microcystin-exposed subjects in clinical settings.

@article{
 title = {Skin Injury Activates a Rapid TRPV1-Dependent Antiviral Protein Response},
 type = {article},
 year = {2022},
 pages = {2249-2259.e9},
 volume = {142},
 month = {8},
 publisher = {Elsevier B.V.},
 day = {1},
 id = {2f701f2d-5f88-3003-a03a-367ccc28d0f7},
 created = {2025-10-30T12:26:02.141Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:42.375Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity. Antiviral proteins (AVPs) are part of the innate host defense system and provide protection against viral pathogens. How breach of the skin barrier influences innate AVP production remains largely unknown. In this study, we characterized the induction and regulation of AVPs after skin injury and identified a key role of TRPV1 in this process. Transcriptional and phenotypic profiling of cutaneous wounds revealed that skin injury induces high levels of AVPs in both mice and humans. Remarkably, pharmacologic and genetic ablation of TRPV1-mediated nociception abrogated the induction of AVPs, including Oas2, Oasl2, and Isg15 after skin injury in mice. Conversely, stimulation of TRPV1 nociceptors was sufficient to induce AVP production involving the CD301b+ cells‒IL-27‒mediated signaling pathway. Using IL-27 receptor‒knockout mice, we show that IL-27 signaling is required in the induction of AVPs after skin injury. Finally, loss of TRPV1 signaling leads to increased viral infectivity of herpes simplex virus. Together, our data indicate that TRPV1 signaling ensures skin antiviral competence on wounding.},
 bibtype = {article},
 author = {Lei, Vivian and Handfield, Chelsea and Kwock, Jeffery T. and Kirchner, Stephen J. and Lee, Min Jin and Coates, Margaret and Wang, Kaiyuan and Han, Qingjian and Wang, Zilong and Powers, Jennifer G. and Wolfe, Sarah and Corcoran, David L. and Fanelli, Brian and Dadlani, Manoj and Ji, Ru Rong and Zhang, Jennifer Y. and MacLeod, Amanda S.},
 doi = {10.1016/j.jid.2021.11.041},
 journal = {Journal of Investigative Dermatology},
 number = {8}
}

The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity. Antiviral proteins (AVPs) are part of the innate host defense system and provide protection against viral pathogens. How breach of the skin barrier influences innate AVP production remains largely unknown. In this study, we characterized the induction and regulation of AVPs after skin injury and identified a key role of TRPV1 in this process. Transcriptional and phenotypic profiling of cutaneous wounds revealed that skin injury induces high levels of AVPs in both mice and humans. Remarkably, pharmacologic and genetic ablation of TRPV1-mediated nociception abrogated the induction of AVPs, including Oas2, Oasl2, and Isg15 after skin injury in mice. Conversely, stimulation of TRPV1 nociceptors was sufficient to induce AVP production involving the CD301b+ cells‒IL-27‒mediated signaling pathway. Using IL-27 receptor‒knockout mice, we show that IL-27 signaling is required in the induction of AVPs after skin injury. Finally, loss of TRPV1 signaling leads to increased viral infectivity of herpes simplex virus. Together, our data indicate that TRPV1 signaling ensures skin antiviral competence on wounding.

@article{
 title = {Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut},
 type = {article},
 year = {2021},
 keywords = {Enzymes,Metabolomics,Microbial ecology,Microbiome},
 pages = {1367-1382},
 volume = {6},
 websites = {https://www.nature.com/articles/s41564-021-00970-4},
 month = {10},
 publisher = {Nature Publishing Group},
 day = {21},
 id = {0dffff8a-fb11-37a6-a2ec-88d3742a6f24},
 created = {2025-07-07T13:25:30.140Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:15.771Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host–microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH). The ability of Bifidobacterium species to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degrading Bifidobacterium species containing the ALDH, including Bifidobacterium longum, B. breve and B. bifidum. We further demonstrate that faecal concentrations of Bifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4+ T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA3). Our findings reveal that breastmilk-promoted Bifidobacterium species produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life. Bifidobacterium species associated with breastfeeding can convert aromatic amino acids into their respective aromatic lactic acids via a previously uncharacterized aromatic lactate dehydrogenase, which may impact immune function in infants.},
 bibtype = {article},
 author = {Laursen, Martin F. and Sakanaka, Mikiyasu and von Burg, Nicole and Mörbe, Urs and Andersen, Daniel and Moll, Janne Marie and Pekmez, Ceyda T. and Rivollier, Aymeric and Michaelsen, Kim F. and Mølgaard, Christian and Lind, Mads Vendelbo and Dragsted, Lars O. and Katayama, Takane and Frandsen, Henrik L. and Vinggaard, Anne Marie and Bahl, Martin I. and Brix, Susanne and Agace, William and Licht, Tine R. and Roager, Henrik M.},
 doi = {10.1038/s41564-021-00970-4},
 journal = {Nature Microbiology 2021 6:11},
 number = {11}
}

Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host–microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH). The ability of Bifidobacterium species to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degrading Bifidobacterium species containing the ALDH, including Bifidobacterium longum, B. breve and B. bifidum. We further demonstrate that faecal concentrations of Bifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4+ T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA3). Our findings reveal that breastmilk-promoted Bifidobacterium species produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life. Bifidobacterium species associated with breastfeeding can convert aromatic amino acids into their respective aromatic lactic acids via a previously uncharacterized aromatic lactate dehydrogenase, which may impact immune function in infants.

@article{
 title = {Crowding reshapes the mucosal but not the systemic response repertoires of Atlantic salmon to peracetic acid},
 type = {article},
 year = {2021},
 keywords = {Amoebic gill disease,Crowding stress,Hydrogen peroxide,Mucosal health,Oxidative stress,Peracetic acid},
 pages = {735830},
 volume = {531},
 month = {1},
 publisher = {Elsevier},
 day = {30},
 id = {585309cf-42de-34c7-bbfb-b95f494c3620},
 created = {2025-07-07T13:25:30.458Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:30.458Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Knowledge of the impact of aquaculture chemotherapeutants on fish physiology is scarce. This is particularly relevant for peracetic acid (PAA), a widely used oxidative disinfectant in aquaculture. The chemical behaviour in water is well studied but knowledge about the physiological consequences for fish is limited. The present study investigated the transcriptomics, morphology, and physiology of Atlantic salmon (Salmo salar) responses to PAA and explored how crowding prior to exposure influenced these responses. Post-smolts were subjected to crowding by reducing the water volume thereby increasing the density for 1 h before they were exposed to 4.8 ppm PAA for 30 min. The exposed fish were allowed to recover for 2 weeks (w), with samplings carried out at 4 h and 2 w post-exposure (p.e.). There were four treatment groups in total: no crowding/control; no crowding/PAA; crowding/control; and crowding/PAA. The physiological changes were documented at the mucosal (i.e., skin and gills) and systemic (i.e., plasma) levels. The overall external welfare score was in good status in all experimental groups. The treatments did not dramatically affect the number of mucous cells in both the skin and the gills. Branchial histomorphology was in a fairly good condition, despite the increased occurrence of epithelial lifting in the crowded groups at 2 w p.e. The gill transcriptome was affected by crowding, PAA, and their combinations more than the skin, as manifested by the number of differentially expressed genes (DEG) in the former. In general, individual stimuli and their combinations elicited strong transcriptional responses in the gills at 4 h p.e. and a marked recovery was observed 2 w thereafter. Crowding altered the dynamics of transcriptional response to PAA especially at 4 h p.e. and the two mucosal tissues demonstrated a contrasting profile – a higher number of DEGs in the gills without crowding history, while higher skin DEGs were observed in the group subjected to crowding prior to exposure. Plasma metabolomics identified 639 compounds, and the metabolomic changes were affected mainly by crowding and sampling time, and not by PAA exposure. The results revealed the ability of salmon to mobilise physiological countermeasures to PAA exposure that were differentially influenced by crowding, and that such an effect was remarkably exhibited at the mucosa rather than in the circulating metabolome.},
 bibtype = {article},
 author = {Lazado, Carlo C. and Sveen, Lene R. and Soleng, Malene and Pedersen, Lars Flemming and Timmerhaus, Gerrit},
 doi = {10.1016/J.AQUACULTURE.2020.735830},
 journal = {Aquaculture}
}

Knowledge of the impact of aquaculture chemotherapeutants on fish physiology is scarce. This is particularly relevant for peracetic acid (PAA), a widely used oxidative disinfectant in aquaculture. The chemical behaviour in water is well studied but knowledge about the physiological consequences for fish is limited. The present study investigated the transcriptomics, morphology, and physiology of Atlantic salmon (Salmo salar) responses to PAA and explored how crowding prior to exposure influenced these responses. Post-smolts were subjected to crowding by reducing the water volume thereby increasing the density for 1 h before they were exposed to 4.8 ppm PAA for 30 min. The exposed fish were allowed to recover for 2 weeks (w), with samplings carried out at 4 h and 2 w post-exposure (p.e.). There were four treatment groups in total: no crowding/control; no crowding/PAA; crowding/control; and crowding/PAA. The physiological changes were documented at the mucosal (i.e., skin and gills) and systemic (i.e., plasma) levels. The overall external welfare score was in good status in all experimental groups. The treatments did not dramatically affect the number of mucous cells in both the skin and the gills. Branchial histomorphology was in a fairly good condition, despite the increased occurrence of epithelial lifting in the crowded groups at 2 w p.e. The gill transcriptome was affected by crowding, PAA, and their combinations more than the skin, as manifested by the number of differentially expressed genes (DEG) in the former. In general, individual stimuli and their combinations elicited strong transcriptional responses in the gills at 4 h p.e. and a marked recovery was observed 2 w thereafter. Crowding altered the dynamics of transcriptional response to PAA especially at 4 h p.e. and the two mucosal tissues demonstrated a contrasting profile – a higher number of DEGs in the gills without crowding history, while higher skin DEGs were observed in the group subjected to crowding prior to exposure. Plasma metabolomics identified 639 compounds, and the metabolomic changes were affected mainly by crowding and sampling time, and not by PAA exposure. The results revealed the ability of salmon to mobilise physiological countermeasures to PAA exposure that were differentially influenced by crowding, and that such an effect was remarkably exhibited at the mucosa rather than in the circulating metabolome.

@article{
 title = {Impact of dietary propionate on fructose-induced changes in lipid metabolism, gut microbiota and short-chain fatty acids in mice},
 type = {article},
 year = {2021},
 keywords = {SCFA},
 pages = {160-173},
 volume = {72},
 websites = {https://www.tandfonline.com/doi/abs/10.1080/09637486.2020.1773415},
 publisher = {Taylor & Francis},
 id = {8a0c9adc-f256-353d-8222-7663d785c1cd},
 created = {2025-07-07T13:25:30.771Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:30.771Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The intake of fructose added to food has dramatically increased in the past few decades (Alwahsh and Gebhardt 2017). The consumption of excessive fructose has been associated with a series of detri...},
 bibtype = {article},
 author = {Brütting, Christine and Lara Bisch, Milena and Brandsch, Corinna and Hirche, Frank and Stangl, Gabriele I.},
 doi = {10.1080/09637486.2020.1773415},
 journal = {International Journal of Food Sciences and Nutrition},
 number = {2}
}

The intake of fructose added to food has dramatically increased in the past few decades (Alwahsh and Gebhardt 2017). The consumption of excessive fructose has been associated with a series of detri...

@article{
 title = {Publisher Correction: Inhibition of succinate dehydrogenase activity impairs human T cell activation and function},
 type = {article},
 year = {2021},
 keywords = {polar},
 volume = {11},
 websites = {https://pubmed.ncbi.nlm.nih.gov/33875757/},
 month = {12},
 publisher = {Sci Rep},
 day = {1},
 id = {24aa7391-76bb-38ab-a4d3-f2f8f0460bcc},
 created = {2025-07-07T13:25:31.129Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:16.215Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The Author Contributions section in this Article is incorrect. “A.W.-O. and C.N. designed the research. C.N. performed experiments, analysed and interpreted the data, made the figures, and wrote the original draft of the paper. A.W.-O. performed microarray analysis. K.D. and M.D. performed metabolome analysis. C.N., A.W.-O., K.D., S.L.F, A.S.Ø.G., T.B.B., M.G., M.D., C.M.B., C.G., T.L., N.Ø. and A.W. reviewed and edited the manuscript. A.W.-O. acquired the funding.”},
 bibtype = {article},
 author = {Nastasi, Claudia and Willerlev-Olsen, Andreas and Dalhoff, Kristoffer and Ford, Shayne L. and Gadsbøll, Anne Sofie Østergaard and Buus, Terkild Brink and Gluud, Maria and Danielsen, Morten and Litman, Thomas and Bonefeld, Charlotte Mennè and Geisler, Carsten and Ødum, Niels and Woetmann, Anders},
 doi = {10.1038/S41598-021-88184-W},
 journal = {Scientific reports},
 number = {1}
}

The Author Contributions section in this Article is incorrect. “A.W.-O. and C.N. designed the research. C.N. performed experiments, analysed and interpreted the data, made the figures, and wrote the original draft of the paper. A.W.-O. performed microarray analysis. K.D. and M.D. performed metabolome analysis. C.N., A.W.-O., K.D., S.L.F, A.S.Ø.G., T.B.B., M.G., M.D., C.M.B., C.G., T.L., N.Ø. and A.W. reviewed and edited the manuscript. A.W.-O. acquired the funding.”

@article{
 title = {Inhibition of succinate dehydrogenase activity impairs human T cell activation and function},
 type = {article},
 year = {2021},
 pages = {1458},
 volume = {11},
 websites = {/pmc/articles/PMC7809054/,/pmc/articles/PMC7809054/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809054/},
 month = {12},
 publisher = {Nature Publishing Group},
 day = {1},
 id = {fbc304f3-7a1a-39d5-b008-e83155f051a3},
 created = {2025-07-07T13:25:31.480Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:16.568Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {T cell activation is intimately linked to metabolism, as distinct metabolic requirements support the functional and phenotypical differences between quiescent and activated T cells. Metabolic transition from mitochondrial oxidative phosphorylation to aerobic glycolysis is crucial for a proper T cell activation. However, the role of tricarboxylic acid cycle (TCA), and in particular succinate dehydrogenase (SDH) in activated T cells needs further elucidation. Here we show that inhibition of SDH during activation of T cells results in strong impairment of proliferation, expression of activation markers, and production of key inflammatory cytokines, despite a concomitant increase in glycolytic metabolic activity. Similar effect of SDH inhibition were demonstrated in pre-activated T cell. Interestingly, itaconic acid, an endogenous SDH inhibitor released from activated macrophages and dendritic cells, had no immunomodulator effect. Taken together, our findings demonstrate that SDH enzyme fitness is critical for mounting and maintaining appropriate activation and function of human T cells.},
 bibtype = {article},
 author = {Nastasi, Claudia and Willerlev-Olsen, Andreas and Dalhoff, Kristoffer and Ford, Shayne L. and Gadsbøll, Anne Sofie Østergaard and Buus, Terkild Brink and Gluud, Maria and Danielsen, Morten and Litman, Thomas and Bonefeld, Charlotte Mennè and Geisler, Carsten and Ødum, Niels and Woetmann, Anders},
 doi = {10.1038/S41598-020-80933-7},
 journal = {Scientific Reports},
 number = {1},
 keywords = {polar}
}

T cell activation is intimately linked to metabolism, as distinct metabolic requirements support the functional and phenotypical differences between quiescent and activated T cells. Metabolic transition from mitochondrial oxidative phosphorylation to aerobic glycolysis is crucial for a proper T cell activation. However, the role of tricarboxylic acid cycle (TCA), and in particular succinate dehydrogenase (SDH) in activated T cells needs further elucidation. Here we show that inhibition of SDH during activation of T cells results in strong impairment of proliferation, expression of activation markers, and production of key inflammatory cytokines, despite a concomitant increase in glycolytic metabolic activity. Similar effect of SDH inhibition were demonstrated in pre-activated T cell. Interestingly, itaconic acid, an endogenous SDH inhibitor released from activated macrophages and dendritic cells, had no immunomodulator effect. Taken together, our findings demonstrate that SDH enzyme fitness is critical for mounting and maintaining appropriate activation and function of human T cells.

@article{
 title = {Cyclic CMP and cyclic UMP mediate bacterial immunity against phages},
 type = {article},
 year = {2021},
 keywords = {nucelotides,polar},
 pages = {5728-5739.e16},
 volume = {184},
 websites = {http://www.cell.com/article/S0092867421011144/fulltext,http://www.cell.com/article/S0092867421011144/abstract,https://www.cell.com/cell/abstract/S0092-8674(21)01114-4},
 month = {11},
 publisher = {Elsevier B.V.},
 day = {11},
 id = {7f9b4b6e-3ee1-3420-ba72-bf039b4a6f06},
 created = {2025-07-07T13:25:31.839Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:16.904Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The cyclic pyrimidines 3′,5′-cyclic cytidine monophosphate (cCMP) and 3′,5′-cyclic uridine monophosphate (cUMP) have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP), which are second messenger molecules with well-established regulatory roles across all domains of life, the biological role of cyclic pyrimidines has remained unclear. Here we report that cCMP and cUMP are second messengers functioning in bacterial immunity against viruses. We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection and demonstrate that these molecules activate immune effectors that execute an antiviral response. A crystal structure of a uridylate cyclase enzyme from this family explains the molecular mechanism of selectivity for pyrimidines as cyclization substrates. Defense systems encoding pyrimidine cyclases, denoted here Pycsar (pyrimidine cyclase system for antiphage resistance), are widespread in prokaryotes. Our results assign clear biological function to cCMP and cUMP as immunity signaling molecules in bacteria.},
 bibtype = {article},
 author = {Tal, Nitzan and Morehouse, Benjamin R. and Millman, Adi and Stokar-Avihail, Avigail and Avraham, Carmel and Fedorenko, Taya and Yirmiya, Erez and Herbst, Ehud and Brandis, Alexander and Mehlman, Tevie and Oppenheimer-Shaanan, Yaara and Keszei, Alexander F.A. and Shao, Sichen and Amitai, Gil and Kranzusch, Philip J. and Sorek, Rotem},
 doi = {10.1016/j.cell.2021.09.031},
 journal = {Cell},
 number = {23}
}

The cyclic pyrimidines 3′,5′-cyclic cytidine monophosphate (cCMP) and 3′,5′-cyclic uridine monophosphate (cUMP) have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP), which are second messenger molecules with well-established regulatory roles across all domains of life, the biological role of cyclic pyrimidines has remained unclear. Here we report that cCMP and cUMP are second messengers functioning in bacterial immunity against viruses. We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection and demonstrate that these molecules activate immune effectors that execute an antiviral response. A crystal structure of a uridylate cyclase enzyme from this family explains the molecular mechanism of selectivity for pyrimidines as cyclization substrates. Defense systems encoding pyrimidine cyclases, denoted here Pycsar (pyrimidine cyclase system for antiphage resistance), are widespread in prokaryotes. Our results assign clear biological function to cCMP and cUMP as immunity signaling molecules in bacteria.

@article{
 title = {Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium},
 type = {article},
 year = {2021},
 keywords = {Immune response,Metabolomics,Virology},
 volume = {24},
 websites = {http://www.cell.com/article/S2589004221012694/fulltext,http://www.cell.com/article/S2589004221012694/abstract,https://www.cell.com/iscience/abstract/S2589-0042(21)01269-4},
 month = {11},
 publisher = {Elsevier Inc.},
 day = {19},
 id = {03764b58-c469-33bd-b86e-0faea19d0fc2},
 created = {2025-07-07T13:25:32.184Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:17.262Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway epithelium and are important human pathogens. The metabolic changes induced by these viruses in a physiologically relevant human model and how this affects innate immune responses to limit viral propagation are not well known. Using an ex vivo model of pseudostratified primary human airway epithelium, we here demonstrate that infection with both IAV and SARS-CoV-2 resulted in distinct metabolic changes including increases in lactate dehydrogenase A (LDHA) expression and LDHA-mediated lactate formation. Interestingly, LDHA regulated both basal and induced mitochondrial anti-viral signaling protein (MAVS)-dependent type I interferon (IFN) responses to promote IAV, but not SARS-CoV-2, replication. Our data demonstrate that LDHA and lactate promote IAV but not SARS-CoV-2 replication by inhibiting MAVS-dependent induction of type I IFN in primary human airway epithelium.},
 bibtype = {article},
 author = {Thyrsted, Jacob and Storgaard, Jacob and Blay-Cadanet, Julia and Heinz, Alexander and Thielke, Anne Laugaard and Crotta, Stefania and de Paoli, Frank and Olagnier, David and Wack, Andreas and Hiller, Karsten and Hansen, Anne Louise and Holm, Christian Kanstrup},
 doi = {10.1016/j.isci.2021.103300},
 journal = {iScience},
 number = {11}
}

Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway epithelium and are important human pathogens. The metabolic changes induced by these viruses in a physiologically relevant human model and how this affects innate immune responses to limit viral propagation are not well known. Using an ex vivo model of pseudostratified primary human airway epithelium, we here demonstrate that infection with both IAV and SARS-CoV-2 resulted in distinct metabolic changes including increases in lactate dehydrogenase A (LDHA) expression and LDHA-mediated lactate formation. Interestingly, LDHA regulated both basal and induced mitochondrial anti-viral signaling protein (MAVS)-dependent type I interferon (IFN) responses to promote IAV, but not SARS-CoV-2, replication. Our data demonstrate that LDHA and lactate promote IAV but not SARS-CoV-2 replication by inhibiting MAVS-dependent induction of type I IFN in primary human airway epithelium.

@article{
 title = {Non-canonical glutamine transamination sustains efferocytosis by coupling redox buffering to oxidative phosphorylation},
 type = {article},
 year = {2021},
 keywords = {Atherosclerosis,Chronic inflammation,Metabolic diseases,Phagocytes},
 pages = {1313-1326},
 volume = {3},
 websites = {https://www.nature.com/articles/s42255-021-00471-y},
 month = {10},
 publisher = {Nature Publishing Group},
 day = {14},
 id = {4da999c6-8149-31c7-9fe4-47801cb4f8b8},
 created = {2025-07-07T13:25:32.511Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:32.511Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Macrophages rely on tightly integrated metabolic rewiring to clear dying neighboring cells by efferocytosis during homeostasis and disease. Here we reveal that glutaminase-1-mediated glutaminolysis is critical to promote apoptotic cell clearance by macrophages during homeostasis in mice. In addition, impaired macrophage glutaminolysis exacerbates atherosclerosis, a condition during which, efficient apoptotic cell debris clearance is critical to limit disease progression. Glutaminase-1 expression strongly correlates with atherosclerotic plaque necrosis in patients with cardiovascular diseases. High-throughput transcriptional and metabolic profiling reveals that macrophage efferocytic capacity relies on a non-canonical transaminase pathway, independent from the traditional requirement of glutamate dehydrogenase to fuel ɑ-ketoglutarate-dependent immunometabolism. This pathway is necessary to meet the unique requirements of efferocytosis for cellular detoxification and high-energy cytoskeletal rearrangements. Thus, we uncover a role for non-canonical glutamine metabolism for efficient clearance of dying cells and maintenance of tissue homeostasis during health and disease in mouse and humans. Merlin et al. find that non-canonical glutamine transamination is required for macrophage efferocytosis in atherosclerotic plaques by sustaining redox buffering and fueling energy production for cytoskeletal rearrangements.},
 bibtype = {article},
 author = {Merlin, Johanna and Ivanov, Stoyan and Dumont, Adélie and Sergushichev, Alexey and Gall, Julie and Stunault, Marion and Ayrault, Marion and Vaillant, Nathalie and Castiglione, Alexia and Swain, Amanda and Orange, Francois and Gallerand, Alexandre and Berton, Thierry and Martin, Jean Charles and Carobbio, Stefania and Masson, Justine and Gaisler-Salomon, Inna and Maechler, Pierre and Rayport, Stephen and Sluimer, Judith C. and Biessen, Erik A.L. and Guinamard, Rodolphe R. and Gautier, Emmanuel L. and Thorp, Edward B. and Artyomov, Maxim N. and Yvan-Charvet, Laurent},
 doi = {10.1038/s42255-021-00471-y},
 journal = {Nature Metabolism 2021 3:10},
 number = {10}
}

Macrophages rely on tightly integrated metabolic rewiring to clear dying neighboring cells by efferocytosis during homeostasis and disease. Here we reveal that glutaminase-1-mediated glutaminolysis is critical to promote apoptotic cell clearance by macrophages during homeostasis in mice. In addition, impaired macrophage glutaminolysis exacerbates atherosclerosis, a condition during which, efficient apoptotic cell debris clearance is critical to limit disease progression. Glutaminase-1 expression strongly correlates with atherosclerotic plaque necrosis in patients with cardiovascular diseases. High-throughput transcriptional and metabolic profiling reveals that macrophage efferocytic capacity relies on a non-canonical transaminase pathway, independent from the traditional requirement of glutamate dehydrogenase to fuel ɑ-ketoglutarate-dependent immunometabolism. This pathway is necessary to meet the unique requirements of efferocytosis for cellular detoxification and high-energy cytoskeletal rearrangements. Thus, we uncover a role for non-canonical glutamine metabolism for efficient clearance of dying cells and maintenance of tissue homeostasis during health and disease in mouse and humans. Merlin et al. find that non-canonical glutamine transamination is required for macrophage efferocytosis in atherosclerotic plaques by sustaining redox buffering and fueling energy production for cytoskeletal rearrangements.

@article{
 title = {Host Stress Signals Stimulate Pneumococcal Transition from Colonization to Dissemination into the Lungs},
 type = {article},
 year = {2021},
 keywords = {MCF},
 volume = {12},
 websites = {https://pubmed.ncbi.nlm.nih.gov/34696596/},
 month = {12},
 publisher = {mBio},
 day = {1},
 id = {a2d4f572-0989-3e5a-99f9-7c68dd26e2af},
 created = {2025-07-07T13:25:32.840Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:32.840Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Streptococcus pneumoniae is an asymptomatic colonizer of the nasopharynx, but it is also one of the most important bacterial pathogens of humans, causing a wide range of mild to life-threatening diseases. The basis of the pneumococcal transition from a commensal to a parasitic lifestyle is not fully understood. We hypothesize that exposure to host catecholamine stress hormones is important for this transition. In this study, we demonstrated that pneumococci preexposed to a hormone released during stress, norepinephrine (NE), have an increased capacity to translocate from the nasopharynx into the lungs compared to untreated pneumococci. Examination of NE-treated pneumococci revealed major alterations in metabolic profiles, cell associations, capsule synthesis, and cell size. By systemically mutating all 12 two-component and 1 orphan regulatory systems, we also identified a unique genetic regulatory circuit involved in pneumococcal recognition and responsiveness to human stress hormones. IMPORTANCE Microbes acquire unique lifestyles under different environmental conditions. Although this is a widespread occurrence, our knowledge of the importance of various host signals and their impact on microbial behavior is not clear despite the therapeutic value of this knowledge. We discovered that catecholamine stress hormones are the host signals that trigger the passage of Streptococcus pneumoniae from a commensal to a parasitic state. We identify that stress hormone treatment of this microbe leads to reductions in cell size and capsule synthesis and renders it more able to migrate from the nasopharynx into the lungs in a mouse model of infection. The microbe requires the TCS09 protein for the recognition and processing of stress hormone signals. Our work has particular clinical significance as catecholamines are abundant in upper respiratory fluids as well as being administered therapeutically to reduce inflammation in ventilated patients, which may explain why intubation in the critically ill is a recognized risk factor for the development of pneumococcal pneumonia.},
 bibtype = {article},
 author = {Alghofaili, Fayez and Najmuldeen, Hastyar and Kareem, Banaz O. and Shlla, Bushra and Fernandes, Vitor E. and Danielsen, Morten and Ketley, Julian M. and Freestone, Primrose and Yesilkaya, Hasan},
 doi = {10.1128/MBIO.02569-21},
 journal = {mBio},
 number = {6}
}

Streptococcus pneumoniae is an asymptomatic colonizer of the nasopharynx, but it is also one of the most important bacterial pathogens of humans, causing a wide range of mild to life-threatening diseases. The basis of the pneumococcal transition from a commensal to a parasitic lifestyle is not fully understood. We hypothesize that exposure to host catecholamine stress hormones is important for this transition. In this study, we demonstrated that pneumococci preexposed to a hormone released during stress, norepinephrine (NE), have an increased capacity to translocate from the nasopharynx into the lungs compared to untreated pneumococci. Examination of NE-treated pneumococci revealed major alterations in metabolic profiles, cell associations, capsule synthesis, and cell size. By systemically mutating all 12 two-component and 1 orphan regulatory systems, we also identified a unique genetic regulatory circuit involved in pneumococcal recognition and responsiveness to human stress hormones. IMPORTANCE Microbes acquire unique lifestyles under different environmental conditions. Although this is a widespread occurrence, our knowledge of the importance of various host signals and their impact on microbial behavior is not clear despite the therapeutic value of this knowledge. We discovered that catecholamine stress hormones are the host signals that trigger the passage of Streptococcus pneumoniae from a commensal to a parasitic state. We identify that stress hormone treatment of this microbe leads to reductions in cell size and capsule synthesis and renders it more able to migrate from the nasopharynx into the lungs in a mouse model of infection. The microbe requires the TCS09 protein for the recognition and processing of stress hormone signals. Our work has particular clinical significance as catecholamines are abundant in upper respiratory fluids as well as being administered therapeutically to reduce inflammation in ventilated patients, which may explain why intubation in the critically ill is a recognized risk factor for the development of pneumococcal pneumonia.

@article{
 title = {The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome},
 type = {article},
 year = {2021},
 keywords = {semi-polar},
 volume = {13},
 websites = {https://pubmed.ncbi.nlm.nih.gov/34836092/},
 month = {11},
 publisher = {Nutrients},
 day = {1},
 id = {1ebf521d-ed7e-3553-b841-d9e13a7638ed},
 created = {2025-07-07T13:25:33.222Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:17.811Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-Nneotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (βdiversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.},
 bibtype = {article},
 author = {Iribarren, Cristina and Magnusson, Maria K. and Vigsnæs, Louise K. and Aziz, Imran and Amundsen, Ingvild Dybdrodt and Šuligoj, Tanja and Juge, Nathalie and Patel, Piyush and Sapnara, Maria and Johnsen, Lea and Sørensen, Nikolaj and Sundin, Johanna and Törnblom, Hans and Simrén, Magnus and Öhman, Lena},
 doi = {10.3390/NU13113836},
 journal = {Nutrients},
 number = {11}
}

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-Nneotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (βdiversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.

@article{
 title = {Effector-mediated membrane disruption controls cell death in CBASS antiphage defense},
 type = {article},
 year = {2021},
 keywords = {nucelotides,polar},
 pages = {5039-5051.e5},
 volume = {81},
 websites = {https://pubmed.ncbi.nlm.nih.gov/34784509/},
 month = {12},
 publisher = {Mol Cell},
 day = {16},
 id = {52da013f-cd64-3668-ba6c-d58ce6c8ba56},
 created = {2025-07-07T13:25:33.544Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:18.200Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Cyclic oligonucleotide-based antiphage signaling systems (CBASS) are antiviral defense operons that protect bacteria from phage replication. Here, we discover a widespread class of CBASS transmembrane (TM) effector proteins that respond to antiviral nucleotide signals and limit phage propagation through direct membrane disruption. Crystal structures of the Yersinia TM effector Cap15 reveal a compact 8-stranded β-barrel scaffold that forms a cyclic dinucleotide receptor domain that oligomerizes upon activation. We demonstrate that activated Cap15 relocalizes throughout the cell and specifically induces rupture of the inner membrane. Screening for active effectors, we identify the function of distinct families of CBASS TM effectors and demonstrate that cell death via disruption of inner-membrane integrity is a common mechanism of defense. Our results reveal the function of the most prominent class of effector protein in CBASS immunity and define disruption of the inner membrane as a widespread strategy of abortive infection in bacterial phage defense.},
 bibtype = {article},
 author = {Duncan-Lowey, Brianna and McNamara-Bordewick, Nora K. and Tal, Nitzan and Sorek, Rotem and Kranzusch, Philip J.},
 doi = {10.1016/J.MOLCEL.2021.10.020},
 journal = {Molecular cell},
 number = {24}
}

Cyclic oligonucleotide-based antiphage signaling systems (CBASS) are antiviral defense operons that protect bacteria from phage replication. Here, we discover a widespread class of CBASS transmembrane (TM) effector proteins that respond to antiviral nucleotide signals and limit phage propagation through direct membrane disruption. Crystal structures of the Yersinia TM effector Cap15 reveal a compact 8-stranded β-barrel scaffold that forms a cyclic dinucleotide receptor domain that oligomerizes upon activation. We demonstrate that activated Cap15 relocalizes throughout the cell and specifically induces rupture of the inner membrane. Screening for active effectors, we identify the function of distinct families of CBASS TM effectors and demonstrate that cell death via disruption of inner-membrane integrity is a common mechanism of defense. Our results reveal the function of the most prominent class of effector protein in CBASS immunity and define disruption of the inner membrane as a widespread strategy of abortive infection in bacterial phage defense.

@article{
 title = {Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer},
 type = {article},
 year = {2021},
 keywords = {SCFA},
 volume = {12},
 websites = {https://pubmed.ncbi.nlm.nih.gov/34210970/},
 month = {12},
 publisher = {Nat Commun},
 day = {1},
 id = {5aa65f60-a638-305e-99ce-ff6c628cb40d},
 created = {2025-07-07T13:25:33.884Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:18.529Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Emerging data demonstrate that the activity of immune cells can be modulated by microbial molecules. Here, we show that the short-chain fatty acids (SCFAs) pentanoate and butyrate enhance the anti-tumor activity of cytotoxic T lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells through metabolic and epigenetic reprograming. We show that in vitro treatment of CTLs and CAR T cells with pentanoate and butyrate increases the function of mTOR as a central cellular metabolic sensor, and inhibits class I histone deacetylase activity. This reprogramming results in elevated production of effector molecules such as CD25, IFN-γ and TNF-α, and significantly enhances the anti-tumor activity of antigen-specific CTLs and ROR1-targeting CAR T cells in syngeneic murine melanoma and pancreatic cancer models. Our data shed light onto microbial molecules that may be used for enhancing cellular anti-tumor immunity. Collectively, we identify pentanoate and butyrate as two SCFAs with therapeutic utility in the context of cellular cancer immunotherapy.},
 bibtype = {article},
 author = {Luu, Maik and Riester, Zeno and Baldrich, Adrian and Reichardt, Nicole and Yuille, Samantha and Busetti, Alessandro and Klein, Matthias and Wempe, Anne and Leister, Hanna and Raifer, Hartmann and Picard, Felix and Muhammad, Khalid and Ohl, Kim and Romero, Rossana and Fischer, Florence and Bauer, Christian A. and Huber, Magdalena and Gress, Thomas M. and Lauth, Matthias and Danhof, Sophia and Bopp, Tobias and Nerreter, Thomas and Mulder, Imke E. and Steinhoff, Ulrich and Hudecek, Michael and Visekruna, Alexander},
 doi = {10.1038/S41467-021-24331-1},
 journal = {Nature communications},
 number = {1}
}

Emerging data demonstrate that the activity of immune cells can be modulated by microbial molecules. Here, we show that the short-chain fatty acids (SCFAs) pentanoate and butyrate enhance the anti-tumor activity of cytotoxic T lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells through metabolic and epigenetic reprograming. We show that in vitro treatment of CTLs and CAR T cells with pentanoate and butyrate increases the function of mTOR as a central cellular metabolic sensor, and inhibits class I histone deacetylase activity. This reprogramming results in elevated production of effector molecules such as CD25, IFN-γ and TNF-α, and significantly enhances the anti-tumor activity of antigen-specific CTLs and ROR1-targeting CAR T cells in syngeneic murine melanoma and pancreatic cancer models. Our data shed light onto microbial molecules that may be used for enhancing cellular anti-tumor immunity. Collectively, we identify pentanoate and butyrate as two SCFAs with therapeutic utility in the context of cellular cancer immunotherapy.

@article{
 title = {Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense},
 type = {article},
 year = {2021},
 keywords = {nucleotides,polar},
 pages = {109206},
 volume = {35},
 month = {6},
 publisher = {Cell Press},
 day = {1},
 id = {e8119c6a-9ef0-3fd9-aade-ceadf9d53d42},
 created = {2025-07-07T13:25:34.222Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:18.901Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are signaling proteins that initiate antiviral immunity in animal cells and cyclic-oligonucleotide-based anti-phage signaling system (CBASS) phage defense in bacteria. Upon phage recognition, bacterial CD-NTases catalyze synthesis of cyclic-oligonucleotide signals, which activate downstream effectors and execute cell death. How CD-NTases control nucleotide selection to specifically induce defense remains poorly defined. Here, we combine structural and nucleotide-analog interference-mapping approaches to identify molecular rules controlling CD-NTase specificity. Structures of the cyclic trinucleotide synthase Enterobacter cloacae CdnD reveal coordinating nucleotide interactions and a possible role for inverted nucleobase positioning during product synthesis. We demonstrate that correct nucleotide selection in the CD-NTase donor pocket results in the formation of a thermostable-protein-nucleotide complex, and we extend our analysis to establish specific patterns governing selectivity for each of the major bacterial CD-NTase clades A–H. Our results explain CD-NTase specificity and enable predictions of nucleotide second-messenger signals within diverse antiviral systems.},
 bibtype = {article},
 author = {Govande, Apurva A. and Duncan-Lowey, Brianna and Eaglesham, James B. and Whiteley, Aaron T. and Kranzusch, Philip J.},
 doi = {10.1016/J.CELREP.2021.109206},
 journal = {Cell Reports},
 number = {9}
}

cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are signaling proteins that initiate antiviral immunity in animal cells and cyclic-oligonucleotide-based anti-phage signaling system (CBASS) phage defense in bacteria. Upon phage recognition, bacterial CD-NTases catalyze synthesis of cyclic-oligonucleotide signals, which activate downstream effectors and execute cell death. How CD-NTases control nucleotide selection to specifically induce defense remains poorly defined. Here, we combine structural and nucleotide-analog interference-mapping approaches to identify molecular rules controlling CD-NTase specificity. Structures of the cyclic trinucleotide synthase Enterobacter cloacae CdnD reveal coordinating nucleotide interactions and a possible role for inverted nucleobase positioning during product synthesis. We demonstrate that correct nucleotide selection in the CD-NTase donor pocket results in the formation of a thermostable-protein-nucleotide complex, and we extend our analysis to establish specific patterns governing selectivity for each of the major bacterial CD-NTase clades A–H. Our results explain CD-NTase specificity and enable predictions of nucleotide second-messenger signals within diverse antiviral systems.

@article{
 title = {Identification of potential citrate metabolism pathways in carnobacterium maltaromaticum},
 type = {article},
 year = {2021},
 keywords = {MCF},
 pages = {2169},
 volume = {9},
 websites = {https://www.mdpi.com/2076-2607/9/10/2169/htm,https://www.mdpi.com/2076-2607/9/10/2169},
 month = {10},
 publisher = {MDPI},
 day = {1},
 id = {fe313604-dc45-3fa1-8e56-1ef4cbda8aaf},
 created = {2025-07-07T13:25:34.610Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:19.241Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {In the present study, we describe the identification of potential citrate metabolism pathways for the lactic acid bacterium (LAB) Carnobacterium maltaromaticum. A phenotypic assay indicated that four of six C. maltaromaticum strains showed weak (Cm 6-1 and ATCC 35586) or even delayed (Cm 3-1 and Cm 5-1) citrate utilization activity. The remaining two strains, Cm 4-1 and Cm 1-2 gave negative results. Additional analysis showed no or very limited utilization of citrate in media containing 1% glucose and 22 or 30 mM citrate and inoculated with Cm 6-1 or ATCC 35586. Two potential pathways of citrate metabolism were identified by bioinformatics analyses in C. maltaromaticum including either oxaloacetate (pathway 1) or tricarboxylic compounds such as isocitrate and α-ketoglutarate (pathway 2) as intermediates. Genes encoding pathway 1 were present in two out of six strains while pathway 2 included genes present in all six strains. The two potential citrate metabolism pathways in C. maltaromaticum may potentially affect the sensory profiles of milk and soft cheeses subjected to growth with this species.},
 bibtype = {article},
 author = {Li, Heng and Ramia, Nancy E. and Borges, Frédéric and Revol-Junelles, Anne Marie and Vogensen, Finn Kvist and Leisner, Jørgen J.},
 doi = {10.3390/MICROORGANISMS9102169/S1},
 journal = {Microorganisms},
 number = {10}
}

In the present study, we describe the identification of potential citrate metabolism pathways for the lactic acid bacterium (LAB) Carnobacterium maltaromaticum. A phenotypic assay indicated that four of six C. maltaromaticum strains showed weak (Cm 6-1 and ATCC 35586) or even delayed (Cm 3-1 and Cm 5-1) citrate utilization activity. The remaining two strains, Cm 4-1 and Cm 1-2 gave negative results. Additional analysis showed no or very limited utilization of citrate in media containing 1% glucose and 22 or 30 mM citrate and inoculated with Cm 6-1 or ATCC 35586. Two potential pathways of citrate metabolism were identified by bioinformatics analyses in C. maltaromaticum including either oxaloacetate (pathway 1) or tricarboxylic compounds such as isocitrate and α-ketoglutarate (pathway 2) as intermediates. Genes encoding pathway 1 were present in two out of six strains while pathway 2 included genes present in all six strains. The two potential citrate metabolism pathways in C. maltaromaticum may potentially affect the sensory profiles of milk and soft cheeses subjected to growth with this species.

@article{
 title = {The ultra-structural, metabolomic and metagenomic characterisation of the sudanese smokeless tobacco 'Toombak'},
 type = {article},
 year = {2021},
 keywords = {Semi-polar,voc},
 pages = {1498-1512},
 volume = {8},
 websites = {https://pubmed.ncbi.nlm.nih.gov/34401360/},
 month = {1},
 publisher = {Toxicol Rep},
 day = {1},
 id = {c5390701-f922-3edc-b43a-8aaf1dc38705},
 created = {2025-07-07T13:25:34.944Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:19.578Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Toombak is a smokeless tobacco produced from the Nicotiana rustica tobacco plant from Sudan. Pre-prepared and ready to buy Toombak samples were analysed using mass spectrometry (heavy metals), gas and liquid chromatography (metabolomics), 16S rRNA metagenomic sequencing (microbiome) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and pH analysis. Chromium, cobalt, and copper were high in the pre-prepared form of Toombak while iron, tobacco specific nitrosamines (TSNAs), formaldehyde and acetaldehyde were high in both types. Firmicutes and Actinobacteria dominated Toombak. Samples of ready to buy Toombak showed inter-variational differences depending on place of purchase. We found Virgibacillus were increased in the pre-prepared form while Corynebacterium casei, Atopococus tabaci, Atopostipes suicloacalis, Oceanobacillus chironomi and Staphylococcus gallinarum were the most abundant species in the ready to buy forms. PICRUSt analysis highlighted increased activity of metal transport systems in the ready to buy samples as well as an antibiotic transport system. SEM-EDX highlighted large non-homogenous, irregular particles with increased sodium, while pH of samples was in the alkaline range. The final composition of Toombak is affected by its method of preparation and the end product has the potential to impart many negative consequences on the health of its users. TSNA levels observed in Toombak were some of the highest in the world while the micro-environment of Toombak supports a distinct microbiota profile.},
 bibtype = {article},
 author = {Sami, Amel and Elimairi, Imad and Patangia, Dhrati and Watkins, Claire and Ryan, C. Anthony and Ross, R. Paul and Stanton, Catherine},
 doi = {10.1016/J.TOXREP.2021.07.008},
 journal = {Toxicology reports}
}

Toombak is a smokeless tobacco produced from the Nicotiana rustica tobacco plant from Sudan. Pre-prepared and ready to buy Toombak samples were analysed using mass spectrometry (heavy metals), gas and liquid chromatography (metabolomics), 16S rRNA metagenomic sequencing (microbiome) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and pH analysis. Chromium, cobalt, and copper were high in the pre-prepared form of Toombak while iron, tobacco specific nitrosamines (TSNAs), formaldehyde and acetaldehyde were high in both types. Firmicutes and Actinobacteria dominated Toombak. Samples of ready to buy Toombak showed inter-variational differences depending on place of purchase. We found Virgibacillus were increased in the pre-prepared form while Corynebacterium casei, Atopococus tabaci, Atopostipes suicloacalis, Oceanobacillus chironomi and Staphylococcus gallinarum were the most abundant species in the ready to buy forms. PICRUSt analysis highlighted increased activity of metal transport systems in the ready to buy samples as well as an antibiotic transport system. SEM-EDX highlighted large non-homogenous, irregular particles with increased sodium, while pH of samples was in the alkaline range. The final composition of Toombak is affected by its method of preparation and the end product has the potential to impart many negative consequences on the health of its users. TSNA levels observed in Toombak were some of the highest in the world while the micro-environment of Toombak supports a distinct microbiota profile.

@article{
 title = {An integrative understanding of the large metabolic shifts induced by antibiotics in critical illness},
 type = {article},
 year = {2021},
 keywords = {BA,SCFA},
 volume = {13},
 websites = {https://pubmed.ncbi.nlm.nih.gov/34793277/},
 publisher = {Gut Microbes},
 id = {b07d62d8-7bfe-34da-b4c4-9c9416f0875b},
 created = {2025-07-07T13:25:35.294Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:35.294Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Antibiotics are commonly used in the Intensive Care Unit (ICU); however, several studies showed that the impact of antibiotics to prevent infection, multi-organ failure, and death in the ICU is less clear than their benefit on course of infection in the absence of organ dysfunction. We characterized here the compositional and metabolic changes of the gut microbiome induced by critical illness and antibiotics in a cohort of 75 individuals in conjunction with 2,180 gut microbiome samples representing 16 different diseases. We revealed an “infection-vulnerable” gut microbiome environment present only in critically ill treated with antibiotics (ICU+). Feeding of Caenorhabditis elegans with Bifidobacterium animalis and Lactobacillus crispatus, species that expanded in ICU+ patients, revealed a significant negative impact of these microbes on host viability and developmental homeostasis. These results suggest that antibiotic administration can dramatically impact essential functional activities in the gut related to immune responses more than critical illness itself, which might explain in part untoward effects of antibiotics in the critically ill.},
 bibtype = {article},
 author = {Marfil-Sánchez, Andrea and Zhang, Lu and Alonso-Pernas, Pol and Mirhakkak, Mohammad and Mueller, Melinda and Seelbinder, Bastian and Ni, Yueqiong and Santhanam, Rakesh and Busch, Anne and Beemelmanns, Christine and Ermolaeva, Maria and Bauer, Michael and Panagiotou, Gianni},
 doi = {10.1080/19490976.2021.1993598},
 journal = {Gut microbes},
 number = {1}
}

Antibiotics are commonly used in the Intensive Care Unit (ICU); however, several studies showed that the impact of antibiotics to prevent infection, multi-organ failure, and death in the ICU is less clear than their benefit on course of infection in the absence of organ dysfunction. We characterized here the compositional and metabolic changes of the gut microbiome induced by critical illness and antibiotics in a cohort of 75 individuals in conjunction with 2,180 gut microbiome samples representing 16 different diseases. We revealed an “infection-vulnerable” gut microbiome environment present only in critically ill treated with antibiotics (ICU+). Feeding of Caenorhabditis elegans with Bifidobacterium animalis and Lactobacillus crispatus, species that expanded in ICU+ patients, revealed a significant negative impact of these microbes on host viability and developmental homeostasis. These results suggest that antibiotic administration can dramatically impact essential functional activities in the gut related to immune responses more than critical illness itself, which might explain in part untoward effects of antibiotics in the critically ill.

@article{
 title = {Antiviral activity of bacterial TIR domains via immune signalling molecules},
 type = {article},
 year = {2021},
 keywords = {polar},
 pages = {116-120},
 volume = {600},
 websites = {https://pubmed.ncbi.nlm.nih.gov/34853457/},
 month = {12},
 publisher = {Nature},
 day = {2},
 id = {05c4da46-ce3b-35ed-83aa-05b6203fb5a5},
 created = {2025-07-07T13:25:35.627Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:35.627Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems1,2. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule that is a variant of cyclic ADP-ribose3,4. This molecule is hypothesized to mediate plant cell death through a pathway that has yet to be resolved5. TIR domains have also been shown to be involved in a bacterial anti-phage defence system called Thoeris6, but the mechanism of Thoeris defence remained unknown. Here we show that phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose. This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death. We also show that, similar to eukaryotic innate immune systems, bacterial TIR-domain proteins determine the immunological specificity to the invading pathogen. Our results describe an antiviral signalling pathway in bacteria, and suggest that the generation of intracellular signalling molecules is an ancient immunological function of TIR domains that is conserved in both plant and bacterial immunity.},
 bibtype = {article},
 author = {Ofir, Gal and Herbst, Ehud and Baroz, Maya and Cohen, Daniel and Millman, Adi and Doron, Shany and Tal, Nitzan and Malheiro, Daniel B.A. and Malitsky, Sergey and Amitai, Gil and Sorek, Rotem},
 doi = {10.1038/S41586-021-04098-7},
 journal = {Nature},
 number = {7887}
}

The Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems1,2. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule that is a variant of cyclic ADP-ribose3,4. This molecule is hypothesized to mediate plant cell death through a pathway that has yet to be resolved5. TIR domains have also been shown to be involved in a bacterial anti-phage defence system called Thoeris6, but the mechanism of Thoeris defence remained unknown. Here we show that phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose. This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death. We also show that, similar to eukaryotic innate immune systems, bacterial TIR-domain proteins determine the immunological specificity to the invading pathogen. Our results describe an antiviral signalling pathway in bacteria, and suggest that the generation of intracellular signalling molecules is an ancient immunological function of TIR domains that is conserved in both plant and bacterial immunity.

@article{
 title = {The Kynurenine Pathway Is Upregulated by Methyl-deficient Diet and Changes Are Averted by Probiotics},
 type = {article},
 year = {2021},
 keywords = {MCF},
 volume = {65},
 websites = {https://pubmed.ncbi.nlm.nih.gov/33686786/},
 month = {5},
 publisher = {Mol Nutr Food Res},
 day = {1},
 id = {4fd04669-b25c-3ad8-8249-63dbbac45bcf},
 created = {2025-07-07T13:25:35.965Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:35.965Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Scope: Probiotics exert immunomodulatory effects and may influence tryptophan metabolism in the host. Deficiency of nutrients related to C1 metabolism might stimulate inflammation by enhancing the kynurenine pathway. This study used Sprague Dawley rats to investigate whether a methyl-deficient diet (MDD) may influence tryptophan/kynurenine pathways and cytokines and whether probiotics can mitigate these effects. Methods and Results: Rats are fed a control or MDD diet. Animals on the MDD diet received vehicle, probiotics (L. helveticus R0052 and B. longum R0175), choline, or probiotics + choline for 10 weeks (n = 10 per group). Concentrations of plasma kynurenine metabolites and the methylation and inflammatory markers in plasma and liver are measured. Results: MDD animals (vs controls) show upregulation of plasma kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyxanthranilic acid, quinolinic acid, nicotinic acid, and nicotinamide (all p < 0.05). In the MDD rats, the probiotics (vs vehicle) cause lower anthranilic acid and a trend towards lower kynurenic acid and picolinic acid. Compared to probiotics alone, probiotics + choline is associated with a reduced enrichment of the bacterial strains in cecum. The interventions have no effect on inflammatory markers. Conclusions: Probiotics counterbalance the effect of MDD diet and downregulate downstream metabolites of the kynurenine pathway.},
 bibtype = {article},
 author = {Tillmann, Sandra and Awwad, Hussain M. and MacPherson, Chad W. and Happ, Denise F. and Treccani, Giulia and Geisel, Juergen and Tompkins, Thomas A. and Ueland, Per Magne and Wegener, Gregers and Obeid, Rima},
 doi = {10.1002/MNFR.202100078},
 journal = {Molecular nutrition & food research},
 number = {9}
}

Scope: Probiotics exert immunomodulatory effects and may influence tryptophan metabolism in the host. Deficiency of nutrients related to C1 metabolism might stimulate inflammation by enhancing the kynurenine pathway. This study used Sprague Dawley rats to investigate whether a methyl-deficient diet (MDD) may influence tryptophan/kynurenine pathways and cytokines and whether probiotics can mitigate these effects. Methods and Results: Rats are fed a control or MDD diet. Animals on the MDD diet received vehicle, probiotics (L. helveticus R0052 and B. longum R0175), choline, or probiotics + choline for 10 weeks (n = 10 per group). Concentrations of plasma kynurenine metabolites and the methylation and inflammatory markers in plasma and liver are measured. Results: MDD animals (vs controls) show upregulation of plasma kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyxanthranilic acid, quinolinic acid, nicotinic acid, and nicotinamide (all p < 0.05). In the MDD rats, the probiotics (vs vehicle) cause lower anthranilic acid and a trend towards lower kynurenic acid and picolinic acid. Compared to probiotics alone, probiotics + choline is associated with a reduced enrichment of the bacterial strains in cecum. The interventions have no effect on inflammatory markers. Conclusions: Probiotics counterbalance the effect of MDD diet and downregulate downstream metabolites of the kynurenine pathway.

@article{
 title = {Skin dysbiosis in the microbiome in atopic dermatitis is site-specific and involves bacteria, fungus and virus},
 type = {article},
 year = {2021},
 keywords = {Atopic dermatitis,Skin microbiome,Dysbiosis,atopic dermatitis,bjerre,correspondence,dk,dybboe,dysbiosis,regionh,rie,skin microbiome},
 pages = {256},
 volume = {21},
 websites = {https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-021-02302-2},
 month = {12},
 publisher = {BMC Microbiology},
 day = {23},
 id = {0237aa18-c8d1-3d03-9cda-4ee537d3a270},
 created = {2025-07-07T13:25:36.301Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:20.191Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Bjerre, Rie Dybboe and Holm, Jacob Bak and Palleja, Albert and Sølberg, Julie and Skov, Lone and Johansen, Jeanne Duus},
 doi = {10.1186/s12866-021-02302-2},
 journal = {BMC Microbiology},
 number = {1}
}

@article{
 title = {Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism},
 type = {article},
 year = {2021},
 pages = {1093},
 volume = {12},
 websites = {http://www.nature.com/articles/s41467-021-21408-9},
 month = {12},
 day = {17},
 id = {dbde0b75-96d6-3abf-a606-c59f342485bc},
 created = {2025-07-07T13:25:36.735Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:20.570Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus -based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu -based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3 + RORγt + IL-17 + ) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.},
 bibtype = {article},
 author = {Jensen, Benjamin A H and Holm, Jacob B and Larsen, Ida S and von Burg, Nicole and Derer, Stefanie and Sonne, Si B and Pærregaard, Simone I and Damgaard, Mads V and Indrelid, Stine A and Rivollier, Aymeric and Agrinier, Anne-laure and Sulek, Karolina and Arnoldussen, Yke J and Fjære, Even and Marette, André and Angell, Inga L and Rudi, Knut and Treebak, Jonas T and Madsen, Lise and Åkesson, Caroline Piercey and Agace, William and Sina, Christian and Kleiveland, Charlotte R and Kristiansen, Karsten and Lea, Tor E},
 doi = {10.1038/s41467-021-21408-9},
 journal = {Nature Communications},
 number = {1}
}

Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus -based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu -based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3 + RORγt + IL-17 + ) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.

@article{
 title = {Dispersal strategies shape persistence and evolution of human gut bacteria},
 type = {article},
 year = {2021},
 keywords = {antibiotics,bacterial dispersal,gut microbiome,metagenomics,population genetics,strain resolution},
 pages = {1167-1176.e9},
 volume = {29},
 month = {7},
 publisher = {Cell Press},
 day = {14},
 id = {2b28bf13-81df-394d-bfe1-e51088318229},
 created = {2025-10-30T12:05:02.991Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:09.312Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Human gut bacterial strains can co-exist with their hosts for decades, but little is known about how these microbes persist and disperse, and evolve thereby. Here, we examined these processes in 5,278 adult and infant fecal metagenomes, longitudinally sampled in individuals and families. Our analyses revealed that a subset of gut species is extremely persistent in individuals, families, and geographic regions, represented often by locally successful strains of the phylum Bacteroidota. These “tenacious” bacteria show high levels of genetic adaptation to the human host but a high probability of loss upon antibiotic interventions. By contrast, heredipersistent bacteria, notably Firmicutes, often rely on dispersal strategies with weak phylogeographic patterns but strong family transmissions, likely related to sporulation. These analyses describe how different dispersal strategies can lead to the long-term persistence of human gut microbes with implications for gut flora modulations.},
 bibtype = {article},
 author = {Hildebrand, Falk and Gossmann, Toni I. and Frioux, Clémence and Özkurt, Ezgi and Myers, Pernille Neve and Ferretti, Pamela and Kuhn, Michael and Bahram, Mohammad and Nielsen, Henrik Bjørn and Bork, Peer},
 doi = {10.1016/J.CHOM.2021.05.008},
 journal = {Cell Host and Microbe},
 number = {7}
}

Human gut bacterial strains can co-exist with their hosts for decades, but little is known about how these microbes persist and disperse, and evolve thereby. Here, we examined these processes in 5,278 adult and infant fecal metagenomes, longitudinally sampled in individuals and families. Our analyses revealed that a subset of gut species is extremely persistent in individuals, families, and geographic regions, represented often by locally successful strains of the phylum Bacteroidota. These “tenacious” bacteria show high levels of genetic adaptation to the human host but a high probability of loss upon antibiotic interventions. By contrast, heredipersistent bacteria, notably Firmicutes, often rely on dispersal strategies with weak phylogeographic patterns but strong family transmissions, likely related to sporulation. These analyses describe how different dispersal strategies can lead to the long-term persistence of human gut microbes with implications for gut flora modulations.

@article{
 title = {Skin dysbiosis in the microbiome in atopic dermatitis is site-specific and involves bacteria, fungus and virus},
 type = {article},
 year = {2021},
 keywords = {Atopic dermatitis,Dysbiosis,Skin microbiome},
 volume = {21},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {b3cfd269-8be1-3a1e-9699-3646b9127e50},
 created = {2025-10-30T12:05:02.991Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:13.048Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Microbial dysbiosis with increased Staphylococcus aureus (S. aureus) colonization on the skin is a hallmark of atopic dermatitis (AD), however most microbiome studies focus on bacteria in the flexures and the microbial composition at other body sites have not been studied systematically. Objectives: The aim of the study is to characterize the skin microbiome, including bacteria, fungi and virus, at different body sites in relation to AD, lesional state, and S. aureus colonization, and to test whether the nares could be a reservoir for S. aureus strain colonization. Methods: Using shotgun metagenomics we characterized microbial compositions from 14 well defined skin sites from 10 patients with AD and 5 healthy controls. Results: We found clear differences in microbial composition between AD and controls at multiple skin sites, most pronounced on the flexures and neck. The flexures exhibited lower alpha-diversity and were colonized by S. aureus, accompanied by S. epidermidis in lesions. Malassezia species were absent on the neck in AD. Virus mostly constituted Propionibacterium and Staphylococcusphages, with increased abundance of Propionibacterium phages PHL041 and PHL092 and Staphylococcus epidermidis phages CNPH82 and PH15 in AD. In lesional samples, both the genus Staphylococcus and Staphylococcus phages were more abundant. S. aureus abundance was higher across all skin sites except from the feet. In samples where S. aureus was highly abundant, lower abundances of S. hominis and Cutibacterium acnes were observed. M. osloensis and M. luteus were more abundant in AD. By single nucleotide variant analysis of S. aureus we found strains to be subject specific. On skin sites some S. aureus strains were similar and some dissimilar to the ones in the nares. Conclusions: Our data indicate a global and site-specific dysbiosis in AD, involving both bacteria, fungus and virus. When defining targeted treatment clinicians should both consider the individual and skin site and future research into potential crosstalk between microbiota in AD yields high potential.},
 bibtype = {article},
 author = {Bjerre, Rie Dybboe and Holm, Jacob Bak and Palleja, Albert and Sølberg, Julie and Skov, Lone and Johansen, Jeanne Duus},
 doi = {10.1186/S12866-021-02302-2},
 journal = {BMC Microbiology},
 number = {1}
}

Background: Microbial dysbiosis with increased Staphylococcus aureus (S. aureus) colonization on the skin is a hallmark of atopic dermatitis (AD), however most microbiome studies focus on bacteria in the flexures and the microbial composition at other body sites have not been studied systematically. Objectives: The aim of the study is to characterize the skin microbiome, including bacteria, fungi and virus, at different body sites in relation to AD, lesional state, and S. aureus colonization, and to test whether the nares could be a reservoir for S. aureus strain colonization. Methods: Using shotgun metagenomics we characterized microbial compositions from 14 well defined skin sites from 10 patients with AD and 5 healthy controls. Results: We found clear differences in microbial composition between AD and controls at multiple skin sites, most pronounced on the flexures and neck. The flexures exhibited lower alpha-diversity and were colonized by S. aureus, accompanied by S. epidermidis in lesions. Malassezia species were absent on the neck in AD. Virus mostly constituted Propionibacterium and Staphylococcusphages, with increased abundance of Propionibacterium phages PHL041 and PHL092 and Staphylococcus epidermidis phages CNPH82 and PH15 in AD. In lesional samples, both the genus Staphylococcus and Staphylococcus phages were more abundant. S. aureus abundance was higher across all skin sites except from the feet. In samples where S. aureus was highly abundant, lower abundances of S. hominis and Cutibacterium acnes were observed. M. osloensis and M. luteus were more abundant in AD. By single nucleotide variant analysis of S. aureus we found strains to be subject specific. On skin sites some S. aureus strains were similar and some dissimilar to the ones in the nares. Conclusions: Our data indicate a global and site-specific dysbiosis in AD, involving both bacteria, fungus and virus. When defining targeted treatment clinicians should both consider the individual and skin site and future research into potential crosstalk between microbiota in AD yields high potential.

@article{
 title = {Gut Microbiota Perturbation in IgA Deficiency Is Influenced by IgA-Autoantibody Status},
 type = {article},
 year = {2021},
 keywords = {Autoimmunity,Functional Profiling of the Gut Microbiota,Immunoglobulin A,Quantitative Metagenomics,Strain-Level Analysis},
 pages = {2423-2434.e5},
 volume = {160},
 month = {6},
 publisher = {W.B. Saunders},
 day = {1},
 id = {e2f1d468-d9eb-36b8-a643-67ddd7159693},
 created = {2025-10-30T12:05:02.993Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:08.160Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background & Aims: IgA exerts its primary function at mucosal surfaces, where it binds microbial antigens to regulate bacterial growth and epithelial attachment. One third of individuals with IgA deficiency (IgAD) suffers from recurrent mucosal infections, possibly related to an altered microbiota. We aimed to delineate the impact of IgAD and the IgA-autoantibody status on the composition and functional capacity of the gut microbiota. Methods: We performed a paired, lifestyle-balanced analysis of the effect of IgA on the gut microbiota composition and functionality based on fecal samples from individuals with IgAD and IgA-sufficient household members (n = 100), involving quantitative shotgun metagenomics, species-centric functional annotation of gut bacteria, and strain-level analyses. We supplemented the data set with 32 individuals with IgAD and examined the influence of IgA-autoantibody status on the composition and functionality of the gut microbiota. Results: The gut microbiota of individuals with IgAD exhibited decreased richness and diversity and was enriched for bacterial species encoding pathogen-related functions including multidrug and antimicrobial peptide resistance, virulence factors, and type III and VI secretion systems. These functional changes were largely attributed to Escherichia coli but were independent of E coli strain variations and most prominent in individuals with IgAD with IgA-specific autoreactive antibodies. Conclusions: The microbiota of individuals with IgAD is enriched for species holding increased proinflammatory potential, thereby potentially decreasing the resistance to gut barrier–perturbing events. This phenotype is especially pronounced in individuals with IgAD with IgA-specific autoreactive antibodies, thus warranting a screening for IgA-specific autoreactive antibodies in IgAD to identify patients with IgAD with increased risk for gastrointestinal implications.},
 bibtype = {article},
 author = {Moll, Janne Marie and Myers, Pernille Neve and Zhang, Chenchen and Eriksen, Carsten and Wolf, Johannes and Appelberg, K. Sofia and Lindberg, Greger and Bahl, Martin Iain and Zhao, Hui and Pan-Hammarström, Qiang and Cai, Kaiye and Jia, Huijue and Borte, Stephan and Nielsen, H. Bjørn and Kristiansen, Karsten and Brix, Susanne and Hammarström, Lennart},
 doi = {10.1053/J.GASTRO.2021.02.053},
 journal = {Gastroenterology},
 number = {7}
}

Background & Aims: IgA exerts its primary function at mucosal surfaces, where it binds microbial antigens to regulate bacterial growth and epithelial attachment. One third of individuals with IgA deficiency (IgAD) suffers from recurrent mucosal infections, possibly related to an altered microbiota. We aimed to delineate the impact of IgAD and the IgA-autoantibody status on the composition and functional capacity of the gut microbiota. Methods: We performed a paired, lifestyle-balanced analysis of the effect of IgA on the gut microbiota composition and functionality based on fecal samples from individuals with IgAD and IgA-sufficient household members (n = 100), involving quantitative shotgun metagenomics, species-centric functional annotation of gut bacteria, and strain-level analyses. We supplemented the data set with 32 individuals with IgAD and examined the influence of IgA-autoantibody status on the composition and functionality of the gut microbiota. Results: The gut microbiota of individuals with IgAD exhibited decreased richness and diversity and was enriched for bacterial species encoding pathogen-related functions including multidrug and antimicrobial peptide resistance, virulence factors, and type III and VI secretion systems. These functional changes were largely attributed to Escherichia coli but were independent of E coli strain variations and most prominent in individuals with IgAD with IgA-specific autoreactive antibodies. Conclusions: The microbiota of individuals with IgAD is enriched for species holding increased proinflammatory potential, thereby potentially decreasing the resistance to gut barrier–perturbing events. This phenotype is especially pronounced in individuals with IgAD with IgA-specific autoreactive antibodies, thus warranting a screening for IgA-specific autoreactive antibodies in IgAD to identify patients with IgAD with increased risk for gastrointestinal implications.

@article{
 title = {Strand Orientation Bias Detector to determine the probability of FFPE sequencing artifacts},
 type = {article},
 year = {2021},
 keywords = {filtering FFPE artifacts,formalin fixation caused mutations,somatic variant calling on FFPE samples},
 volume = {22},
 month = {11},
 publisher = {Oxford University Press},
 day = {1},
 id = {6af87505-2ad4-3bdc-a11e-b620f6801828},
 created = {2025-10-30T12:05:03.007Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:15.233Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Formalin-fixed paraffin-embedded tissue, the most common tissue specimen stored in clinical practice, presents challenges in the analysis due to formalin-induced artifacts. Here, we present Strand Orientation Bias Detector (SOBDetector), a flexible computational platform compatible with all the common somatic SNV-calling pipelines, designed to assess the probability whether a given detected mutation is an artifact. The underlying predictor mechanism is based on the posterior distribution of a Bayesian logistic regression model trained on The Cancer Genome Atlas whole exomes. SOBDetector is a freely available cross-platform program, implemented in Java 1.8.},
 bibtype = {article},
 author = {Diossy, Miklos and Sztupinszki, Zsofia and Krzystanek, Marcin and Borcsok, Judit and Eklund, Aron C. and Csabai, István and Pedersen, Anders Gorm and Szallasi, Zoltan},
 doi = {10.1093/BIB/BBAB186},
 journal = {Briefings in Bioinformatics},
 number = {6}
}

Formalin-fixed paraffin-embedded tissue, the most common tissue specimen stored in clinical practice, presents challenges in the analysis due to formalin-induced artifacts. Here, we present Strand Orientation Bias Detector (SOBDetector), a flexible computational platform compatible with all the common somatic SNV-calling pipelines, designed to assess the probability whether a given detected mutation is an artifact. The underlying predictor mechanism is based on the posterior distribution of a Bayesian logistic regression model trained on The Cancer Genome Atlas whole exomes. SOBDetector is a freely available cross-platform program, implemented in Java 1.8.

@article{
 title = {Microbiome compositions and resistome levels after antibiotic treatment of critically ill patients: An observational cohort study},
 type = {article},
 year = {2021},
 keywords = {Antimicrobial resistance,Antimicrobial treatment,Metagenomics,Microbiome,Microbiota},
 volume = {9},
 month = {12},
 publisher = {MDPI},
 day = {1},
 id = {3e2fadcf-2aa4-39a8-9bf3-858ff150acee},
 created = {2025-10-30T12:05:03.033Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:16.083Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This study aimed to investigate how broad-and narrow-spectrum antibiotics affect the gut microbiome and the resistome in antibiotic naïve patients during neurointensive care. Patients admitted to the neurointensive care unit were treated with broad-spectrum (meropenem or piperacillin/tazobactam) or narrow-spectrum antibiotic treatment (including ciprofloxacin, cefuroxime, vancomycin and dicloxacillin) according to clinical indications. A rectal swab was collected from each patient before and after 5–7 days of antibiotic therapy (N = 34), respectively. Shotgun metagenomic sequencing was performed and the composition of metagenomic species (MGS) was determined. The resistome was characterized with CARD RGI software and the CARD database. As a measure for selection pressure in the patient, we used the sum of the number of days with each antibiotic (antibiotic days). We observed a significant increase in richness and a tendency for an increase in the Shannon index after narrow-spectrum treatment. For broad-spectrum treatment the effect was more diverse, with some patients increasing and some decreasing in richness and Shannon index. This was studied further by comparison of patients who had gained or lost >10 MGS, respectively. Selection pressure was significantly higher in patients with decreased richness and a decreased Shannon index who received the broad treatment. A decrease in MGS richness was significantly correlated to the number of drugs administered and the selection pressure in the patient. Bray–Curtis dissimilarities were significant between the pre-and post-treatment of samples in the narrow group, indicating that the longer the narrow-spectrum treatment, the higher the differences between the pre-and the post-treatment microbial composition. We did not find significant differences between pre-and post-treatment for both antibiotic spectrum treatments; however, we observed that most of the antibiotic class resistance genes were higher in abundance in post-treatment after broad-spectrum treatment.},
 bibtype = {article},
 author = {Nielsen, Karen Leth and Olsen, Markus Harboe and Pallejá, Albert and Ebdrup, Søren Røddik and Sørensen, Nikolaj and Lukjancenko, Oksana and Marvig, Rasmus L. and Møller, Kirsten and Frimodt-Møller, Niels and Hertz, Frederik Boëtius},
 doi = {10.3390/MICROORGANISMS9122542},
 journal = {Microorganisms},
 number = {12}
}

Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This study aimed to investigate how broad-and narrow-spectrum antibiotics affect the gut microbiome and the resistome in antibiotic naïve patients during neurointensive care. Patients admitted to the neurointensive care unit were treated with broad-spectrum (meropenem or piperacillin/tazobactam) or narrow-spectrum antibiotic treatment (including ciprofloxacin, cefuroxime, vancomycin and dicloxacillin) according to clinical indications. A rectal swab was collected from each patient before and after 5–7 days of antibiotic therapy (N = 34), respectively. Shotgun metagenomic sequencing was performed and the composition of metagenomic species (MGS) was determined. The resistome was characterized with CARD RGI software and the CARD database. As a measure for selection pressure in the patient, we used the sum of the number of days with each antibiotic (antibiotic days). We observed a significant increase in richness and a tendency for an increase in the Shannon index after narrow-spectrum treatment. For broad-spectrum treatment the effect was more diverse, with some patients increasing and some decreasing in richness and Shannon index. This was studied further by comparison of patients who had gained or lost >10 MGS, respectively. Selection pressure was significantly higher in patients with decreased richness and a decreased Shannon index who received the broad treatment. A decrease in MGS richness was significantly correlated to the number of drugs administered and the selection pressure in the patient. Bray–Curtis dissimilarities were significant between the pre-and post-treatment of samples in the narrow group, indicating that the longer the narrow-spectrum treatment, the higher the differences between the pre-and the post-treatment microbial composition. We did not find significant differences between pre-and post-treatment for both antibiotic spectrum treatments; however, we observed that most of the antibiotic class resistance genes were higher in abundance in post-treatment after broad-spectrum treatment.

@article{
 title = {Microbiome meta-analysis and cross-disease comparison enabled by the SIAMCAT machine learning toolbox},
 type = {article},
 year = {2021},
 keywords = {Machine learning,Meta-analysis,Microbiome data analysis,Microbiome-wide association studies (MWAS),Statistical modeling},
 volume = {22},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {455ad83a-64a7-345b-8ad4-aaa95b4bbcda},
 created = {2025-10-30T12:05:03.035Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:12.321Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The human microbiome is increasingly mined for diagnostic and therapeutic biomarkers using machine learning (ML). However, metagenomics-specific software is scarce, and overoptimistic evaluation and limited cross-study generalization are prevailing issues. To address these, we developed SIAMCAT, a versatile R toolbox for ML-based comparative metagenomics. We demonstrate its capabilities in a meta-analysis of fecal metagenomic studies (10,803 samples). When naively transferred across studies, ML models lost accuracy and disease specificity, which could however be resolved by a novel training set augmentation strategy. This reveals some biomarkers to be disease-specific, with others shared across multiple conditions. SIAMCAT is freely available from siamcat.embl.de.},
 bibtype = {article},
 author = {Wirbel, Jakob and Zych, Konrad and Essex, Morgan and Karcher, Nicolai and Kartal, Ece and Salazar, Guillem and Bork, Peer and Sunagawa, Shinichi and Zeller, Georg},
 doi = {10.1186/S13059-021-02306-1},
 journal = {Genome Biology},
 number = {1}
}

The human microbiome is increasingly mined for diagnostic and therapeutic biomarkers using machine learning (ML). However, metagenomics-specific software is scarce, and overoptimistic evaluation and limited cross-study generalization are prevailing issues. To address these, we developed SIAMCAT, a versatile R toolbox for ML-based comparative metagenomics. We demonstrate its capabilities in a meta-analysis of fecal metagenomic studies (10,803 samples). When naively transferred across studies, ML models lost accuracy and disease specificity, which could however be resolved by a novel training set augmentation strategy. This reveals some biomarkers to be disease-specific, with others shared across multiple conditions. SIAMCAT is freely available from siamcat.embl.de.

@article{
 title = {Human Milk Oligosaccharides Modulate Fecal Microbiota and Are Safe for Use in Children With Overweight: A Randomized Controlled Trial},
 type = {article},
 year = {2021},
 keywords = {2′-Fucosyllactose,bifidobacteria,gut microbiota,lacto-N-neotetraose},
 pages = {408-414},
 volume = {73},
 month = {9},
 publisher = {Lippincott Williams and Wilkins},
 day = {1},
 id = {ac6b7fe5-846c-3c61-932a-f9c63bc535d9},
 created = {2025-10-30T12:05:03.039Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.039Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Objectives:Human milk oligosaccharides (HMOs) impact the intestinal microbiota by increasing beneficial bacteria in infants and adults, and are safe and well tolerated in these age groups. Effects on intestinal microbiota, safety, and digestive tolerance in children have not been, however, assessed. The aims of this trial were to evaluate if HMOs are able to specifically modulate the intestinal microbiota in children, and to assess safety and digestive tolerance.Methods:In this randomized, double-blinded, placebo-controlled trial, 75 children with overweight (including obesity) ages 6 to 12 years were randomized to receive 2′-fucosyllactose (2′FL), a mix of 2′FL and lacto-N-neotetraose (Mix), or a glucose placebo orally administrated once per day for 8 weeks.Results:The relative abundance of bifidobacteria increased significantly after 4 (P < 0.001) and 8 (P = 0.025) weeks of intervention in the 2′FL-group and after 4 weeks (P = 0.033) in the Mix-group, whereas no change was observed in the placebo group. Compared with placebo, the 2′FL-group had a significant increase in bifidobacteria abundance after 4 weeks (P < 0.001) and 8 weeks (P = 0.010) and the Mix-group showed a tendency to increased bifidobacteria abundance after 4 (P = 0.071) and 8 weeks (P = 0.071). Bifidobacterium adolescentis drove the bifidogenic effect in the 2 groups. Biochemical markers indicated no safety concerns, and the products did not induce digestive tolerance issues as assessed by Gastrointestinal Symptoms Rating Scale and Bristol Stool Form Scale. Conclusions:Both 2′FL and the Mix beneficially modulate intestinal microbiota by increasing bifidobacteria. Furthermore, supplementation with either 2′FL alone or a Mix is safe and well tolerated in children.},
 bibtype = {article},
 author = {Fonvig, Cilius Esmann and Amundsen, Ingvild Dybdrodt and Vigsnæs, Louise Kristine and Sørensen, Nikolaj and Frithioff-Bøjsøe, Christine and Christiansen, Michael and Hedley, Paula Louise and Holm, Louise Aas and McConnell, Bruce and Holm, Jens Christian},
 doi = {10.1097/MPG.0000000000003205},
 journal = {Journal of Pediatric Gastroenterology and Nutrition},
 number = {3}
}

Objectives:Human milk oligosaccharides (HMOs) impact the intestinal microbiota by increasing beneficial bacteria in infants and adults, and are safe and well tolerated in these age groups. Effects on intestinal microbiota, safety, and digestive tolerance in children have not been, however, assessed. The aims of this trial were to evaluate if HMOs are able to specifically modulate the intestinal microbiota in children, and to assess safety and digestive tolerance.Methods:In this randomized, double-blinded, placebo-controlled trial, 75 children with overweight (including obesity) ages 6 to 12 years were randomized to receive 2′-fucosyllactose (2′FL), a mix of 2′FL and lacto-N-neotetraose (Mix), or a glucose placebo orally administrated once per day for 8 weeks.Results:The relative abundance of bifidobacteria increased significantly after 4 (P < 0.001) and 8 (P = 0.025) weeks of intervention in the 2′FL-group and after 4 weeks (P = 0.033) in the Mix-group, whereas no change was observed in the placebo group. Compared with placebo, the 2′FL-group had a significant increase in bifidobacteria abundance after 4 weeks (P < 0.001) and 8 weeks (P = 0.010) and the Mix-group showed a tendency to increased bifidobacteria abundance after 4 (P = 0.071) and 8 weeks (P = 0.071). Bifidobacterium adolescentis drove the bifidogenic effect in the 2 groups. Biochemical markers indicated no safety concerns, and the products did not induce digestive tolerance issues as assessed by Gastrointestinal Symptoms Rating Scale and Bristol Stool Form Scale. Conclusions:Both 2′FL and the Mix beneficially modulate intestinal microbiota by increasing bifidobacteria. Furthermore, supplementation with either 2′FL alone or a Mix is safe and well tolerated in children.

@article{
 title = {Affective disorders impact prevalence of Flavonifractor and abundance of Christensenellaceae in gut microbiota},
 type = {article},
 year = {2021},
 keywords = {Affective disorders,Bipolar disorder,Gut microbiota,High risk,Major depressive disorder,Unaffected relatives},
 volume = {110},
 month = {8},
 publisher = {Elsevier Inc.},
 day = {30},
 id = {28230774-afc3-30f2-a4ea-ca20bdd466d0},
 created = {2025-10-30T12:05:03.042Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:06.650Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background Affective disorders (AD) have been associated with a higher prevalence of the gut Flavonifractor genus and a lower abundance of the gut Christensenellaceae family. Objective and methods By pooling two independent study samples of patients with AD (n = 176), their unaffected first-degree relatives (n = 70) and healthy controls (n = 101) we aimed to replicate and extend our prior findings of differential Flavonifractor prevalence and Christensenellaceae abundance when comparing patients with AD and healthy controls. The gut microbiota was profiled using 16S rRNA gene amplicon sequencing. Results The pattern of higher prevalence of Flavonifractor and lower Centered Log-Ratio (CLR) abundance of Christensenellaceae was associated with AD. In generalized linear models the CLR abundance of Christensenellaceae was lower in patients with AD (p = 0.024), and in smokers (p = 1.9*10−4), and inversely associated with increasing waist circumference (p = 0.031). The prevalence of Flavonifractor was higher in patients with AD (p = 0.033) and in smokers (p = 0.036). No impact of psychotropic medication was found. The CLR abundance of Christensenellaceae (p = 0.041), but not the prevalence of Flavonifractor (p = 0.20) could distinguish non-smoking patients with AD from non-smoking healthy controls, whereas no such associations were found in smokers. Unaffected relatives neither differed from patients with AD nor from healthy controls. Conclusion Compared with findings in healthy controls, AD was associated with a significantly lower CLR abundance of the health-linked Christensenellaceae and a significantly higher prevalence of Flavonifractor; findings that are associated with enhanced oxidative stress and systemic low-grade inflammation. If our observations are validated in future independent studies, they support the notion that parts of aberrant gut microbiota are shared by AD and states of dysmetabolism.},
 bibtype = {article},
 author = {Coello, Klara and Hansen, Tue Haldor and Sørensen, Nikolaj and Ottesen, Ninja Meinhard and Miskowiak, Kamilla Woznica and Pedersen, Oluf and Kessing, Lars Vedel and Vinberg, Maj},
 doi = {10.1016/J.PNPBP.2021.110300},
 journal = {Progress in Neuro-Psychopharmacology and Biological Psychiatry}
}

Background Affective disorders (AD) have been associated with a higher prevalence of the gut Flavonifractor genus and a lower abundance of the gut Christensenellaceae family. Objective and methods By pooling two independent study samples of patients with AD (n = 176), their unaffected first-degree relatives (n = 70) and healthy controls (n = 101) we aimed to replicate and extend our prior findings of differential Flavonifractor prevalence and Christensenellaceae abundance when comparing patients with AD and healthy controls. The gut microbiota was profiled using 16S rRNA gene amplicon sequencing. Results The pattern of higher prevalence of Flavonifractor and lower Centered Log-Ratio (CLR) abundance of Christensenellaceae was associated with AD. In generalized linear models the CLR abundance of Christensenellaceae was lower in patients with AD (p = 0.024), and in smokers (p = 1.9*10−4), and inversely associated with increasing waist circumference (p = 0.031). The prevalence of Flavonifractor was higher in patients with AD (p = 0.033) and in smokers (p = 0.036). No impact of psychotropic medication was found. The CLR abundance of Christensenellaceae (p = 0.041), but not the prevalence of Flavonifractor (p = 0.20) could distinguish non-smoking patients with AD from non-smoking healthy controls, whereas no such associations were found in smokers. Unaffected relatives neither differed from patients with AD nor from healthy controls. Conclusion Compared with findings in healthy controls, AD was associated with a significantly lower CLR abundance of the health-linked Christensenellaceae and a significantly higher prevalence of Flavonifractor; findings that are associated with enhanced oxidative stress and systemic low-grade inflammation. If our observations are validated in future independent studies, they support the notion that parts of aberrant gut microbiota are shared by AD and states of dysmetabolism.

@article{
 title = {Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism},
 type = {article},
 year = {2021},
 volume = {12},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {5c1fb30c-3b83-3964-82e2-c6c66b23032f},
 created = {2025-10-30T12:05:03.050Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:12.718Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.},
 bibtype = {article},
 author = {Jensen, Benjamin A.H. and Holm, Jacob B. and Larsen, Ida S. and von Burg, Nicole and Derer, Stefanie and Sonne, Si B. and Pærregaard, Simone I. and Damgaard, Mads V. and Indrelid, Stine A. and Rivollier, Aymeric and Agrinier, Anne Laure and Sulek, Karolina and Arnoldussen, Yke J. and Fjære, Even and Marette, André and Angell, Inga L. and Rudi, Knut and Treebak, Jonas T. and Madsen, Lise and Åkesson, Caroline Piercey and Agace, William and Sina, Christian and Kleiveland, Charlotte R. and Kristiansen, Karsten and Lea, Tor E.},
 doi = {10.1038/S41467-021-21408-9},
 journal = {Nature Communications},
 number = {1}
}

Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.

@article{
 title = {Fecal microbiota transplantation from overweight or obese donors in cachectic patients with advanced gastroesophageal cancer: A randomized, double-blind, placebo-controlled, Phase II Study},
 type = {article},
 year = {2021},
 pages = {3784-3792},
 volume = {27},
 month = {7},
 publisher = {American Association for Cancer Research Inc.},
 day = {1},
 id = {3ed4d36a-8ed3-39f1-baf0-d7fbf6c87edc},
 created = {2025-10-30T12:05:03.050Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.050Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Purpose: Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer. Experimental Design: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics). Results: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [HR = 0.38; 95% confidence interval (CI), 0.14–1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21–1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota. Conclusions: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.},
 bibtype = {article},
 author = {de Clercq, Nicolien C. and van den Ende, Tom and Prodan, Andrei and Hemke, Robert and Davids, Mark and Pedersen, Helle K. and Nielsen, Henrik B. and Groen, A. K. and de Vos, Willem M. and van Laarhoven, Hanneke W.M. and Nieuwdorp, Max},
 doi = {10.1158/1078-0432.CCR-20-4918},
 journal = {Clinical Cancer Research},
 number = {13}
}

Purpose: Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer. Experimental Design: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics). Results: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [HR = 0.38; 95% confidence interval (CI), 0.14–1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21–1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota. Conclusions: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.

@article{
 title = {Sialylated human milk oligosaccharides program cognitive development through a non-genomic transmission mode},
 type = {article},
 year = {2021},
 pages = {2854-2871},
 volume = {26},
 month = {7},
 publisher = {Springer Nature},
 day = {1},
 id = {86c542d5-c775-3489-b2d8-fec101fc7f33},
 created = {2025-10-30T12:05:03.064Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:10.201Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Breastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1tm2Jxm/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6′SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6′SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6′SL-deficient milk. To test whether lactational 6′SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6′SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6′SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.},
 bibtype = {article},
 author = {Hauser, Jonas and Pisa, Edoardo and Arias Vásquez, Alejandro and Tomasi, Flavio and Traversa, Alice and Chiodi, Valentina and Martin, Francois Pierre and Sprenger, Norbert and Lukjancenko, Oksana and Zollinger, Alix and Metairon, Sylviane and Schneider, Nora and Steiner, Pascal and Martire, Alberto and Caputo, Viviana and Macrì, Simone},
 doi = {10.1038/S41380-021-01054-9},
 journal = {Molecular Psychiatry},
 number = {7}
}

Breastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1tm2Jxm/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6′SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6′SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6′SL-deficient milk. To test whether lactational 6′SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6′SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6′SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.

@article{
 title = {The effects of human milk oligosaccharides on gut microbiota, metabolite profiles and host mucosal response in patients with irritable bowel syndrome},
 type = {article},
 year = {2021},
 keywords = {2′-O-fucosyllactose,Antibacterial response,Gut microenvironment,Human milk oligosaccharides,Irritable bowel syndrome,Lacto-N-neotetraose,Metabolomics,Microbiota},
 volume = {13},
 month = {11},
 publisher = {MDPI},
 day = {1},
 id = {e22a110c-2e6c-3b62-aaf8-b03397659aad},
 created = {2025-10-30T12:05:03.066Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:15.743Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-Nneotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (βdiversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.},
 bibtype = {article},
 author = {Iribarren, Cristina and Magnusson, Maria K. and Vigsnæs, Louise K. and Aziz, Imran and Amundsen, Ingvild Dybdrodt and Šuligoj, Tanja and Juge, Nathalie and Patel, Piyush and Sapnara, Maria and Johnsen, Lea and Sørensen, Nikolaj and Sundin, Johanna and Törnblom, Hans and Simrén, Magnus and Öhman, Lena},
 doi = {10.3390/NU13113836},
 journal = {Nutrients},
 number = {11}
}

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-Nneotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (βdiversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.

@article{
 title = { The Influence of FUT2 and FUT3 Polymorphisms and Nasopharyngeal Microbiome on Respiratory Infections in Breastfed Bangladeshi Infants from the Microbiota and Health Study },
 type = {article},
 year = {2021},
 volume = {6},
 month = {12},
 publisher = {American Society for Microbiology},
 day = {22},
 id = {244d3d0e-2685-37aa-81f2-a12aba3185c8},
 created = {2025-10-30T12:05:03.085Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.085Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The observed risk reduction of acute respiratory infections (ARIs) among infants of secretor mothers during the predominant breastfeeding period is consistent with the hypothesis that fucosylated oligosaccharides in human milk contribute to protection against respiratory infections. Respiratory pathogens were only weak modulators of risk, and the nasopharyngeal microbiome did not influence ARI risk, suggesting that the associated protective effects of human milk oligosaccharides (HMOs) are not conveyed via changes in the nasopharyngeal microbiome. Acute respiratory infections (ARIs) are one of the most common causes of morbidity and mortality in young children. The aim of our study was to examine whether variation in maternal FUT2 (α1,2-fucosyltransferase 2) and FUT3 (α1,3/4-fucosyltransferase 3) genes, which shape fucosylated human milk oligosaccharides (HMOs) in breast milk, are associated with the occurrence of ARIs in breastfed infants as well as the influence of the nasopharyngeal microbiome on ARI risk. Occurrences of ARIs were prospectively recorded in a cohort of 240 breastfed Bangladeshi infants from birth to 2 years. Secretor and Lewis status was established by sequencing of FUT2/3 genes. The nasopharyngeal microbiome was characterized by shotgun metagenomics, complemented by specific detection of respiratory pathogens; 88.6% of mothers and 91% of infants were identified as secretors. Maternal secretor status was associated with reduced ARI incidence among these infants in the period from birth to 6 months (incidence rate ratio [IRR], 0.66; 95% confidence interval [CI], 0.47 to 0.94; P =  0.020), but not at later time periods. The nasopharyngeal microbiome, despite precise characterization to the species level, was not predictive of subsequent ARIs. The observed risk reduction of ARIs among infants of secretor mothers during the predominant breastfeeding period is consistent with the hypothesis that fucosylated oligosaccharides in human milk contribute to protection against respiratory infections. However, we found no evidence that modulation of the nasopharyngeal microbiome influenced ARI risk.  IMPORTANCE The observed risk reduction of acute respiratory infections (ARIs) among infants of secretor mothers during the predominant breastfeeding period is consistent with the hypothesis that fucosylated oligosaccharides in human milk contribute to protection against respiratory infections. Respiratory pathogens were only weak modulators of risk, and the nasopharyngeal microbiome did not influence ARI risk, suggesting that the associated protective effects of human milk oligosaccharides (HMOs) are not conveyed via changes in the nasopharyngeal microbiome. Our observations add to the evidence for a role of fucosylated HMOs in protection against respiratory infections in exclusively or predominantly breastfed infants in low-resource settings. There is no indication that the nasopharyngeal microbiome substantially modulates the risk of subsequent mild ARIs. Larger studies are needed to provide mechanistic insights on links between secretor status, HMOs, and risk of respiratory infections. },
 bibtype = {article},
 author = {Binia, Aristea and Siegwald, Léa and Sultana, Shamima and Shevlyakova, Maya and Lefebvre, Gregory and Foata, Francis and Combremont, Séverine and Charpagne, Aline and Vidal, Karine and Sprenger, Norbert and Rahman, Mahbubar and Palleja, Albert and Eklund, Aron C. and Nielsen, Henrik Bjørn and Brüssow, Harald and Sarker, Shafiqul Alam and Sakwinska, Olga},
 doi = {10.1128/MSPHERE.00686-21},
 journal = {mSphere},
 number = {6}
}

The observed risk reduction of acute respiratory infections (ARIs) among infants of secretor mothers during the predominant breastfeeding period is consistent with the hypothesis that fucosylated oligosaccharides in human milk contribute to protection against respiratory infections. Respiratory pathogens were only weak modulators of risk, and the nasopharyngeal microbiome did not influence ARI risk, suggesting that the associated protective effects of human milk oligosaccharides (HMOs) are not conveyed via changes in the nasopharyngeal microbiome. Acute respiratory infections (ARIs) are one of the most common causes of morbidity and mortality in young children. The aim of our study was to examine whether variation in maternal FUT2 (α1,2-fucosyltransferase 2) and FUT3 (α1,3/4-fucosyltransferase 3) genes, which shape fucosylated human milk oligosaccharides (HMOs) in breast milk, are associated with the occurrence of ARIs in breastfed infants as well as the influence of the nasopharyngeal microbiome on ARI risk. Occurrences of ARIs were prospectively recorded in a cohort of 240 breastfed Bangladeshi infants from birth to 2 years. Secretor and Lewis status was established by sequencing of FUT2/3 genes. The nasopharyngeal microbiome was characterized by shotgun metagenomics, complemented by specific detection of respiratory pathogens; 88.6% of mothers and 91% of infants were identified as secretors. Maternal secretor status was associated with reduced ARI incidence among these infants in the period from birth to 6 months (incidence rate ratio [IRR], 0.66; 95% confidence interval [CI], 0.47 to 0.94; P = 0.020), but not at later time periods. The nasopharyngeal microbiome, despite precise characterization to the species level, was not predictive of subsequent ARIs. The observed risk reduction of ARIs among infants of secretor mothers during the predominant breastfeeding period is consistent with the hypothesis that fucosylated oligosaccharides in human milk contribute to protection against respiratory infections. However, we found no evidence that modulation of the nasopharyngeal microbiome influenced ARI risk. IMPORTANCE The observed risk reduction of acute respiratory infections (ARIs) among infants of secretor mothers during the predominant breastfeeding period is consistent with the hypothesis that fucosylated oligosaccharides in human milk contribute to protection against respiratory infections. Respiratory pathogens were only weak modulators of risk, and the nasopharyngeal microbiome did not influence ARI risk, suggesting that the associated protective effects of human milk oligosaccharides (HMOs) are not conveyed via changes in the nasopharyngeal microbiome. Our observations add to the evidence for a role of fucosylated HMOs in protection against respiratory infections in exclusively or predominantly breastfed infants in low-resource settings. There is no indication that the nasopharyngeal microbiome substantially modulates the risk of subsequent mild ARIs. Larger studies are needed to provide mechanistic insights on links between secretor status, HMOs, and risk of respiratory infections.

@article{
 title = {Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species},
 type = {article},
 year = {2021},
 volume = {11},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {49450158-bedb-35fe-bdb2-09af57bdb6a5},
 created = {2025-10-30T12:05:03.092Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:10.665Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Knowledge about in vivo effects of human circulating C-6 hydroxylated bile acids (BAs), also called muricholic acids, is sparse. It is unsettled if the gut microbiome might contribute to their biosynthesis. Here, we measured a range of serum BAs and related them to markers of human metabolic health and the gut microbiome. We examined 283 non-obese and obese Danish adults from the MetaHit study. Fasting concentrations of serum BAs were quantified using ultra-performance liquid chromatography-tandem mass-spectrometry. The gut microbiome was characterized with shotgun metagenomic sequencing and genome-scale metabolic modeling. We find that tauro- and glycohyocholic acid correlated inversely with body mass index (P = 4.1e-03, P = 1.9e-05, respectively), waist circumference (P = 0.017, P = 1.1e-04, respectively), body fat percentage (P = 2.5e-03, P = 2.3e-06, respectively), insulin resistance (P = 0.051, P = 4.6e-4, respectively), fasting concentrations of triglycerides (P = 0.06, P = 9.2e-4, respectively) and leptin (P = 0.067, P = 9.2e-4). Tauro- and glycohyocholic acids, and tauro-a-muricholic acid were directly linked with a distinct gut microbial community primarily composed of Clostridia species (P = 0.037, P = 0.013, P = 0.027, respectively). We conclude that serum conjugated C-6-hydroxylated BAs associate with measures of human metabolic health and gut communities of Clostridia species. The findings merit preclinical interventions and human feasibility studies to explore the therapeutic potential of these BAs in obesity and type 2 diabetes.},
 bibtype = {article},
 author = {Petersen, Anders and Julienne, Hanna and Hyötyläinen, Tuulia and Sen, Partho and Fan, Yong and Pedersen, Helle Krogh and Jäntti, Sirkku and Hansen, Tue H. and Nielsen, Trine and Jørgensen, Torben and Hansen, Torben and Myers, Pernille Neve and Nielsen, H. Bjørn and Ehrlich, S. Dusko and Orešič, Matej and Pedersen, Oluf},
 doi = {10.1038/S41598-021-91482-Y},
 journal = {Scientific Reports},
 number = {1}
}

Knowledge about in vivo effects of human circulating C-6 hydroxylated bile acids (BAs), also called muricholic acids, is sparse. It is unsettled if the gut microbiome might contribute to their biosynthesis. Here, we measured a range of serum BAs and related them to markers of human metabolic health and the gut microbiome. We examined 283 non-obese and obese Danish adults from the MetaHit study. Fasting concentrations of serum BAs were quantified using ultra-performance liquid chromatography-tandem mass-spectrometry. The gut microbiome was characterized with shotgun metagenomic sequencing and genome-scale metabolic modeling. We find that tauro- and glycohyocholic acid correlated inversely with body mass index (P = 4.1e-03, P = 1.9e-05, respectively), waist circumference (P = 0.017, P = 1.1e-04, respectively), body fat percentage (P = 2.5e-03, P = 2.3e-06, respectively), insulin resistance (P = 0.051, P = 4.6e-4, respectively), fasting concentrations of triglycerides (P = 0.06, P = 9.2e-4, respectively) and leptin (P = 0.067, P = 9.2e-4). Tauro- and glycohyocholic acids, and tauro-a-muricholic acid were directly linked with a distinct gut microbial community primarily composed of Clostridia species (P = 0.037, P = 0.013, P = 0.027, respectively). We conclude that serum conjugated C-6-hydroxylated BAs associate with measures of human metabolic health and gut communities of Clostridia species. The findings merit preclinical interventions and human feasibility studies to explore the therapeutic potential of these BAs in obesity and type 2 diabetes.

@article{
 title = {Improved metagenome binning and assembly using deep variational autoencoders},
 type = {article},
 year = {2021},
 pages = {555-560},
 volume = {39},
 month = {5},
 publisher = {Nature Research},
 day = {1},
 id = {774a22f3-dc6b-3872-b9e0-8a6c0bfd32c0},
 created = {2025-10-30T12:05:03.132Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.132Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Despite recent advances in metagenomic binning, reconstruction of microbial species from metagenomics data remains challenging. Here we develop variational autoencoders for metagenomic binning (VAMB), a program that uses deep variational autoencoders to encode sequence coabundance and k-mer distribution information before clustering. We show that a variational autoencoder is able to integrate these two distinct data types without any previous knowledge of the datasets. VAMB outperforms existing state-of-the-art binners, reconstructing 29–98% and 45% more near-complete (NC) genomes on simulated and real data, respectively. Furthermore, VAMB is able to separate closely related strains up to 99.5% average nucleotide identity (ANI), and reconstructed 255 and 91 NC Bacteroides vulgatus and Bacteroides dorei sample-specific genomes as two distinct clusters from a dataset of 1,000 human gut microbiome samples. We use 2,606 NC bins from this dataset to show that species of the human gut microbiome have different geographical distribution patterns. VAMB can be run on standard hardware and is freely available at https://github.com/RasmussenLab/vamb.},
 bibtype = {article},
 author = {Nissen, Jakob Nybo and Johansen, Joachim and Allesøe, Rosa Lundbye and Sønderby, Casper Kaae and Armenteros, Jose Juan Almagro and Grønbech, Christopher Heje and Jensen, Lars Juhl and Nielsen, Henrik Bjørn and Petersen, Thomas Nordahl and Winther, Ole and Rasmussen, Simon},
 doi = {10.1038/S41587-020-00777-4},
 journal = {Nature Biotechnology},
 number = {5}
}

Despite recent advances in metagenomic binning, reconstruction of microbial species from metagenomics data remains challenging. Here we develop variational autoencoders for metagenomic binning (VAMB), a program that uses deep variational autoencoders to encode sequence coabundance and k-mer distribution information before clustering. We show that a variational autoencoder is able to integrate these two distinct data types without any previous knowledge of the datasets. VAMB outperforms existing state-of-the-art binners, reconstructing 29–98% and 45% more near-complete (NC) genomes on simulated and real data, respectively. Furthermore, VAMB is able to separate closely related strains up to 99.5% average nucleotide identity (ANI), and reconstructed 255 and 91 NC Bacteroides vulgatus and Bacteroides dorei sample-specific genomes as two distinct clusters from a dataset of 1,000 human gut microbiome samples. We use 2,606 NC bins from this dataset to show that species of the human gut microbiome have different geographical distribution patterns. VAMB can be run on standard hardware and is freely available at https://github.com/RasmussenLab/vamb.

@article{
 title = {Advanced dental cleaning is associated with reduced risk of copd exacerbations – a randomized controlled trial},
 type = {article},
 year = {2021},
 keywords = {Alpha diversity,Beta diversity,Health status,Lung function,Periodontal disease,Plaque microbiome},
 pages = {3203-3215},
 volume = {16},
 publisher = {Dove Medical Press Ltd},
 id = {6e32b379-e40a-3030-bbee-0fc2a3a04ca0},
 created = {2025-10-30T12:05:03.319Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:03.319Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Purpose: Infections from the oral microbiome may lead to exacerbations of chronic obstructive pulmonary disease (COPD). We investigated whether advanced dental cleaning could reduce exacerbation frequency. Secondary outcomes were disease-specific health status, lung function, and whether the bacterial load and composition of plaque microbiome at baseline were associated with a difference in outcomes. Patients and Methods: One-hundred-one primary and secondary care patients with COPD were randomized to intervention with advanced dental cleaning or to dental examination only, repeated after six months. At baseline and at 12 months, data of exacerbations, lung function, COPD Assessment Test (CAT) score, and periodontal status were collected from questionnaires, record review, and periodontal examination. Student’s t-test and Mann– Whitney-U (MWU) test compared changes in outcomes. The primary outcome variable was also assessed using multivariable linear regression with adjustment for potential con-founders. Microbiome analyses of plaque samples taken at baseline were performed using Wilcoxon signed ranks tests for calculation of alpha diversity, per mutational multivariate analysis of variance for beta diversity, and receiver operating characteristic curves for prediction of outcomes based on machine learning models. Results: In the MWU test, the annual exacerbation frequency was significantly reduced in patients previously experiencing frequent exacerbations (p = 0.020) and in those with repeated advanced dental cleaning (p = 0.039) compared with the non-treated control group, but not in the total population including both patients with a single and repeated visits (p = 0.207). The result was confirmed in multivariable linear regression, where the risk of new exacerbations was significantly lower in patients both in the intention to treat analysis (regression coefficient 0.36 (95% CI 0.25–0.52), p < 0.0001) and in the population with repeated dental cleaning (0.16 (0.10–0.27), p < 0.0001). The composition of microbiome at baseline was moderately predictive of an increased risk of worsened health status at 12 months (AUC = 0.723). Conclusion: Advanced dental cleaning is associated with a reduced frequency of COPD exacerbations. Regular periodontal examination and dental cleaning may be of clinical importance to prevent COPD exacerbations.},
 bibtype = {article},
 author = {Sundh, Josefin and Tanash, Hanan and Arian, Rahi and Neves-Guimaraes, Alessandra and Broberg, Katrin and Lindved, Gustav and Kern, Timo and Zych, Konrad and Nielsen, Henrik Bjørn and Halling, Anders and Ohlsson, Bodil and Jönsson, Daniel},
 doi = {10.2147/COPD.S327036},
 journal = {International Journal of COPD}
}

Purpose: Infections from the oral microbiome may lead to exacerbations of chronic obstructive pulmonary disease (COPD). We investigated whether advanced dental cleaning could reduce exacerbation frequency. Secondary outcomes were disease-specific health status, lung function, and whether the bacterial load and composition of plaque microbiome at baseline were associated with a difference in outcomes. Patients and Methods: One-hundred-one primary and secondary care patients with COPD were randomized to intervention with advanced dental cleaning or to dental examination only, repeated after six months. At baseline and at 12 months, data of exacerbations, lung function, COPD Assessment Test (CAT) score, and periodontal status were collected from questionnaires, record review, and periodontal examination. Student’s t-test and Mann– Whitney-U (MWU) test compared changes in outcomes. The primary outcome variable was also assessed using multivariable linear regression with adjustment for potential con-founders. Microbiome analyses of plaque samples taken at baseline were performed using Wilcoxon signed ranks tests for calculation of alpha diversity, per mutational multivariate analysis of variance for beta diversity, and receiver operating characteristic curves for prediction of outcomes based on machine learning models. Results: In the MWU test, the annual exacerbation frequency was significantly reduced in patients previously experiencing frequent exacerbations (p = 0.020) and in those with repeated advanced dental cleaning (p = 0.039) compared with the non-treated control group, but not in the total population including both patients with a single and repeated visits (p = 0.207). The result was confirmed in multivariable linear regression, where the risk of new exacerbations was significantly lower in patients both in the intention to treat analysis (regression coefficient 0.36 (95% CI 0.25–0.52), p < 0.0001) and in the population with repeated dental cleaning (0.16 (0.10–0.27), p < 0.0001). The composition of microbiome at baseline was moderately predictive of an increased risk of worsened health status at 12 months (AUC = 0.723). Conclusion: Advanced dental cleaning is associated with a reduced frequency of COPD exacerbations. Regular periodontal examination and dental cleaning may be of clinical importance to prevent COPD exacerbations.

@article{
 title = {The genital microbiome and its potential for detecting sexual assault},
 type = {article},
 year = {2021},
 keywords = {Genital microbiome,Microbial signature,Sexual assault,Whole shotgun sequencing},
 volume = {51},
 month = {3},
 publisher = {Elsevier Ireland Ltd},
 day = {1},
 id = {c298f096-b62b-36da-8863-b94594e76ffb},
 created = {2025-10-30T12:26:00.969Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.969Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Since its inception, the Human Microbiome Project (HMP) has provided key discoveries that can be applied to forensics, in addition to those of obvious medical value. Whether for postmortem interval estimation, geolocation, or human identification, there are many applications of the microbiome as an investigative lead for forensic casework. The human skin microbiome has shown great potential for use in studies of transfer and human identification, however there has been little focus on the genital microbiome, in particular penile skin which differs from other body sites. Our preliminary data on both the penile and vaginal microbiome demonstrates potential value in cases of sexual assault. In this study we describe genital microbial signatures based on the analysis of five male and five female genital samples and compare these results to those from longitudinal studies. Selected taxa, e.g., Gardnerella, Lactobacilli, Finegoldia, Peptoniphilus, and Anaerococci, are shown to be candidate constituents of the genital microbiome that merit investigation for use in sexual assault casework.},
 bibtype = {article},
 author = {Ghemrawi, Mirna and Torres, Andrea Ramírez and Duncan, George and Colwell, Rita and Dadlani, Manoj and McCord, Bruce},
 doi = {10.1016/J.FSIGEN.2020.102432},
 journal = {Forensic Science International: Genetics}
}

Since its inception, the Human Microbiome Project (HMP) has provided key discoveries that can be applied to forensics, in addition to those of obvious medical value. Whether for postmortem interval estimation, geolocation, or human identification, there are many applications of the microbiome as an investigative lead for forensic casework. The human skin microbiome has shown great potential for use in studies of transfer and human identification, however there has been little focus on the genital microbiome, in particular penile skin which differs from other body sites. Our preliminary data on both the penile and vaginal microbiome demonstrates potential value in cases of sexual assault. In this study we describe genital microbial signatures based on the analysis of five male and five female genital samples and compare these results to those from longitudinal studies. Selected taxa, e.g., Gardnerella, Lactobacilli, Finegoldia, Peptoniphilus, and Anaerococci, are shown to be candidate constituents of the genital microbiome that merit investigation for use in sexual assault casework.

@article{
 title = {Unraveling the complex interactions among organisms in the microbiome is necessary to identify unique signatures predicting CD onset},
 type = {article},
 year = {2021},
 volume = {118},
 month = {10},
 publisher = {National Academy of Sciences},
 day = {12},
 id = {76aa023c-f6c2-36f7-b0eb-181965ebfc53},
 created = {2025-10-30T12:26:01.003Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.003Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Leonard, Maureen M. and Colwell, Rita R. and Fasano, Alessio},
 doi = {10.1073/pnas.2114053118},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 number = {41}
}

@article{
 title = {Microbiota and metabolomic patterns in the breast milk of subjects with celiac disease on a gluten-free diet},
 type = {article},
 year = {2021},
 keywords = {Breast milk microbiome,Celiac disease,Multi-omics analysis},
 volume = {13},
 month = {7},
 publisher = {MDPI AG},
 day = {1},
 id = {6e94e4e2-72ac-3052-905e-4634db5dc45c},
 created = {2025-10-30T12:26:01.007Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:06.389Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The intestinal microbiome may trigger celiac disease (CD) in individuals with a genetic disposition when exposed to dietary gluten. Research demonstrates that nutrition during infancy is crucial to the intestinal microbiome engraftment. Very few studies to date have focused on the breast milk composition of subjects with a history of CD on a gluten-free diet. Here, we utilize a multi-omics approach with shotgun metagenomics to analyze the breast milk microbiome integrated with metabolome profiling of 36 subjects, 20 with CD on a gluten-free diet and 16 healthy controls. These analyses identified significant differences in bacterial and viral species/strains and functional pathways but no difference in metabolite abundance. Specifically, three bacterial strains with increased abundance were identified in subjects with CD on a gluten-free diet of which one (Rothia mucilaginosa) has been previously linked to autoimmune conditions. We also identified five pathways with increased abundance in subjects with CD on a gluten-free diet. We additionally found four bacterial and two viral species/strains with increased abundance in healthy controls. Overall, the differences observed in bacterial and viral species/strains and in functional pathways observed in our analysis may influence microbiome engraftment in neonates, which may impact their future clinical outcomes.},
 bibtype = {article},
 author = {Olshan, Katherine L. and Zomorrodi, Ali R. and Pujolassos, Meritxell and Troisi, Jacopo and Khan, Nayeim and Fanelli, Brian and Kenyon, Victoria and Fasano, Alessio and Leonard, Maureen M.},
 doi = {10.3390/NU13072243},
 journal = {Nutrients},
 number = {7}
}

The intestinal microbiome may trigger celiac disease (CD) in individuals with a genetic disposition when exposed to dietary gluten. Research demonstrates that nutrition during infancy is crucial to the intestinal microbiome engraftment. Very few studies to date have focused on the breast milk composition of subjects with a history of CD on a gluten-free diet. Here, we utilize a multi-omics approach with shotgun metagenomics to analyze the breast milk microbiome integrated with metabolome profiling of 36 subjects, 20 with CD on a gluten-free diet and 16 healthy controls. These analyses identified significant differences in bacterial and viral species/strains and functional pathways but no difference in metabolite abundance. Specifically, three bacterial strains with increased abundance were identified in subjects with CD on a gluten-free diet of which one (Rothia mucilaginosa) has been previously linked to autoimmune conditions. We also identified five pathways with increased abundance in subjects with CD on a gluten-free diet. We additionally found four bacterial and two viral species/strains with increased abundance in healthy controls. Overall, the differences observed in bacterial and viral species/strains and in functional pathways observed in our analysis may influence microbiome engraftment in neonates, which may impact their future clinical outcomes.

@article{
 title = {Microbiome signatures of progression toward celiac disease onset in at-risk children in a longitudinal prospective cohort study},
 type = {article},
 year = {2021},
 keywords = {Autoimmunity,Celiac disease,Gut microbiome,Multiomics analysis},
 volume = {118},
 month = {7},
 publisher = {National Academy of Sciences},
 day = {20},
 id = {50983c83-37f3-332d-b248-aafa74b38a8f},
 created = {2025-10-30T12:26:01.009Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.009Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Other than exposure to gluten and genetic compatibility, the gut microbiome has been suggested to be involved in celiac disease (CD) pathogenesis by mediating interactions between gluten/environmental factors and the host immune system. However, to establish disease progression markers, it is essential to assess alterations in the gut microbiota before disease onset. Here, a prospective metagenomic analysis of the gut microbiota of infants at risk of CD was done to track shifts in the microbiota before CD development. We performed cross-sectional and longitudinal analyses of gut microbiota, functional pathways, and metabolites, starting from 18 mo before CD onset, in 10 infants who developed CD and 10 matched nonaffected infants. Cross-sectional analysis at CD onset identified altered abundance of six microbial strains and several metabolites between cases and controls but no change in microbial species or pathway abundance. Conversely, results of longitudinal analysis revealed several microbial species/strains/pathways/metabolites occurring in increased abundance and detected before CD onset. These had previously been linked to autoimmune and inflammatory conditions (e.g., Dialister invisus, Parabacteroides sp., Lachnospiraceae, tryptophan metabolism, and metabolites serine and threonine). Others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects (e.g., Streptococcus thermophilus, Faecalibacterium prausnitzii, and Clostridium clostridioforme). Additionally, we uncovered previously unreported microbes/pathways/ metabolites (e.g., Porphyromonas sp., high mannose–type N-glycan biosynthesis, and serine) that point to CD-specific biomarkers. Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity.},
 bibtype = {article},
 author = {Leonard, Maureen M. and Valitutti, Francesco and Karathia, Hiren and Pujolassos, Meritxell and Kenyon, Victoria and Fanelli, Brian and Troisi, Jacopo and Subramanian, Poorani and Camhi, Stephanie and Colucci, Angelo and Serena, Gloria and Cucchiara, Salvatore and Trovato, Chiara Maria and Malamisura, Basilio and Francavilla, Ruggiero and Elli, Luca and Hasan, Nur A. and Zomorrodi, Ali R. and Colwell, Rita and Fasano, Alessio},
 doi = {10.1073/PNAS.2020322118},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 number = {29}
}

Other than exposure to gluten and genetic compatibility, the gut microbiome has been suggested to be involved in celiac disease (CD) pathogenesis by mediating interactions between gluten/environmental factors and the host immune system. However, to establish disease progression markers, it is essential to assess alterations in the gut microbiota before disease onset. Here, a prospective metagenomic analysis of the gut microbiota of infants at risk of CD was done to track shifts in the microbiota before CD development. We performed cross-sectional and longitudinal analyses of gut microbiota, functional pathways, and metabolites, starting from 18 mo before CD onset, in 10 infants who developed CD and 10 matched nonaffected infants. Cross-sectional analysis at CD onset identified altered abundance of six microbial strains and several metabolites between cases and controls but no change in microbial species or pathway abundance. Conversely, results of longitudinal analysis revealed several microbial species/strains/pathways/metabolites occurring in increased abundance and detected before CD onset. These had previously been linked to autoimmune and inflammatory conditions (e.g., Dialister invisus, Parabacteroides sp., Lachnospiraceae, tryptophan metabolism, and metabolites serine and threonine). Others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects (e.g., Streptococcus thermophilus, Faecalibacterium prausnitzii, and Clostridium clostridioforme). Additionally, we uncovered previously unreported microbes/pathways/ metabolites (e.g., Porphyromonas sp., high mannose–type N-glycan biosynthesis, and serine) that point to CD-specific biomarkers. Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity.

@article{
 title = {Evaluation of a combined multilocus sequence typing and whole-genome sequencing two-step algorithm for routine typing of clostridioides difficile},
 type = {article},
 year = {2021},
 keywords = {Clostridium difficile,MLST,Molecular subtyping,WGS},
 volume = {59},
 month = {2},
 publisher = {American Society for Microbiology},
 day = {1},
 id = {34a99485-90c7-3b36-8f88-9af73cc9c28a},
 created = {2025-10-30T12:26:01.014Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.014Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Multilocus sequence typing (MLST) is a low-resolution but rapid genotyping method for Clostridioides difficile. Whole-genome sequencing (WGS) has emerged as the new gold standard for C. difficile typing, but cost and lack of standardization still limit broad utilization. In this study, we evaluated the potential to combine the portability of MLST with the increased resolution of WGS for a cost-saving approach to routine C. difficile typing. C. difficile strains from two New York City hospitals (hospital A and hospital B) were selected. WGS single-nucleotide polymorphism (wgSNP) was performed using established methods. Sequence types (ST) were determined using PubMLST, while wgSNP analysis was performed using the Bionumerics software. An additional analysis of a subset of data (hospital A) was made comparing the Bionumerics software to the CosmosID pipeline. Cost and turnaround time to results were compared for the algorithmic approach of MLST followed by wgSNP versus direct wgSNP. Among the 202 C. difficile isolates typed, 91% (n = 185/203) clustered within the representative ST, showing a high agreement between MLST and wgSNP. While clustering was similar between the Bionumerics and CosmosID pipelines, large differences in the overall number of SNPs were noted. A two-step algorithm for routine typing results in significantly lower cost than routine use of WGS. Our results suggest that using MLST as a first step in routine typing of C. difficile followed by WGS for MLST concordant strains is a less technically demanding, cost-saving approach for performing C. difficile typing than WGS alone without loss of discriminatory power.},
 bibtype = {article},
 author = {Kamboj, Mini and McMillen, Tracy and Syed, Mustafa and Chow, Hoi Yan and Jani, Krupa and Aslam, Anoshe and Brite, Jennifer and Fanelli, Brian and Hasan, Nur A. and Dadlani, Manoj and Westblade, Lars and Zehir, Ahmet and Simon, Matthew and Babady, N. Esther},
 doi = {10.1128/JCM.01955-20},
 journal = {Journal of Clinical Microbiology},
 number = {2}
}

Multilocus sequence typing (MLST) is a low-resolution but rapid genotyping method for Clostridioides difficile. Whole-genome sequencing (WGS) has emerged as the new gold standard for C. difficile typing, but cost and lack of standardization still limit broad utilization. In this study, we evaluated the potential to combine the portability of MLST with the increased resolution of WGS for a cost-saving approach to routine C. difficile typing. C. difficile strains from two New York City hospitals (hospital A and hospital B) were selected. WGS single-nucleotide polymorphism (wgSNP) was performed using established methods. Sequence types (ST) were determined using PubMLST, while wgSNP analysis was performed using the Bionumerics software. An additional analysis of a subset of data (hospital A) was made comparing the Bionumerics software to the CosmosID pipeline. Cost and turnaround time to results were compared for the algorithmic approach of MLST followed by wgSNP versus direct wgSNP. Among the 202 C. difficile isolates typed, 91% (n = 185/203) clustered within the representative ST, showing a high agreement between MLST and wgSNP. While clustering was similar between the Bionumerics and CosmosID pipelines, large differences in the overall number of SNPs were noted. A two-step algorithm for routine typing results in significantly lower cost than routine use of WGS. Our results suggest that using MLST as a first step in routine typing of C. difficile followed by WGS for MLST concordant strains is a less technically demanding, cost-saving approach for performing C. difficile typing than WGS alone without loss of discriminatory power.

@article{
 title = {Diversity of plasmids and genes encoding resistance to extended‐spectrum β‐lactamase in escherichia coli from different animal sources},
 type = {article},
 year = {2021},
 keywords = {Animal sources,Antimicrobial resistance,Extended‐spectrum β‐lactamase,Multi‐locus sequence typing,Whole-genome sequencing},
 volume = {9},
 month = {5},
 publisher = {MDPI AG},
 day = {1},
 id = {53ce0399-3176-34bf-b012-86c4ceb3c0b0},
 created = {2025-10-30T12:26:01.023Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:11.364Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Antimicrobial resistance associated with the spread of plasmid‐encoded extended-spectrum β‐lactamase (ESBL) genes conferring resistance to third generation cephalosporins is increasing worldwide. However, data on the population of ESBL producing E. coli in different animal sources and their antimicrobial characteristics are limited. The purpose of this study was to investigate potential reservoirs of ESBL‐encoded genes in E. coli isolated from swine, beef, dairy, and poultry collected from different regions of the United States using whole‐genome sequencing (WGS). Three hundred isolates were typed into different phylogroups, characterized by BOX AIR‐ 1 PCR and tested for resistance to antimicrobials. Of the 300 isolates, 59.7% were resistant to sulfisoxazole, 49.3% to tetracycline, 32.3% to cephalothin, 22.3% to ampicillin, 20% to streptomycin, 16% to ticarcillin; resistance to the remaining 12 antimicrobials was less than 10%. Phylogroups A and B1 were most prevalent with A (n = 92, 30%) and B1 (87 = 29%). A total of nine E. coli isolates were confirmed as ESBL producers by double‐disk synergy testing and multidrug resistant (MDR) to at least three antimicrobial drug classes. Using WGS, significantly higher numbers of ESBL‐E. coli were detected in swine and dairy manure than from any other animal sources, suggesting that these may be the primary animal sources for ESBL producing E. coli. These isolates carry plasmids, such as IncFIA(B), IncFII, IncX1, IncX4, IncQ1, CollRNAI, Col440I, and acquired ARGs aph(6)‐Id, aph(3″)‐ Ib,aadA5, aph(3′)‐Ia, blaCTX‐M‐15, blaTEM‐1B, mphA, ermB, catA1, sul1, sul2, tetB, dfrA17. One of the E. coli isolates from swine with ST 410 was resistant to nine antibiotics and carried more than 28 virulence factors, and this ST has been shown to belong to an international high‐risk clone. Our data suggests that ESBL producing E. coli are widely distributed in different animal sources, but swine and dairy cattle may be their main reservoir.},
 bibtype = {article},
 author = {Ibekwe, Abasiofiok and Durso, Lisa and Ducey, Thomas F. and Oladeinde, Adelumola and Jackson, Charlene R. and Frye, Jonathan G. and Dungan, Robert and Moorman, Tom and Brooks, John P. and Obayiuwana, Amarachukwu and Karathia, Hiren and Fanelli, Brian and Hasan, Nur},
 doi = {10.3390/MICROORGANISMS9051057},
 journal = {Microorganisms},
 number = {5}
}

Antimicrobial resistance associated with the spread of plasmid‐encoded extended-spectrum β‐lactamase (ESBL) genes conferring resistance to third generation cephalosporins is increasing worldwide. However, data on the population of ESBL producing E. coli in different animal sources and their antimicrobial characteristics are limited. The purpose of this study was to investigate potential reservoirs of ESBL‐encoded genes in E. coli isolated from swine, beef, dairy, and poultry collected from different regions of the United States using whole‐genome sequencing (WGS). Three hundred isolates were typed into different phylogroups, characterized by BOX AIR‐ 1 PCR and tested for resistance to antimicrobials. Of the 300 isolates, 59.7% were resistant to sulfisoxazole, 49.3% to tetracycline, 32.3% to cephalothin, 22.3% to ampicillin, 20% to streptomycin, 16% to ticarcillin; resistance to the remaining 12 antimicrobials was less than 10%. Phylogroups A and B1 were most prevalent with A (n = 92, 30%) and B1 (87 = 29%). A total of nine E. coli isolates were confirmed as ESBL producers by double‐disk synergy testing and multidrug resistant (MDR) to at least three antimicrobial drug classes. Using WGS, significantly higher numbers of ESBL‐E. coli were detected in swine and dairy manure than from any other animal sources, suggesting that these may be the primary animal sources for ESBL producing E. coli. These isolates carry plasmids, such as IncFIA(B), IncFII, IncX1, IncX4, IncQ1, CollRNAI, Col440I, and acquired ARGs aph(6)‐Id, aph(3″)‐ Ib,aadA5, aph(3′)‐Ia, blaCTX‐M‐15, blaTEM‐1B, mphA, ermB, catA1, sul1, sul2, tetB, dfrA17. One of the E. coli isolates from swine with ST 410 was resistant to nine antibiotics and carried more than 28 virulence factors, and this ST has been shown to belong to an international high‐risk clone. Our data suggests that ESBL producing E. coli are widely distributed in different animal sources, but swine and dairy cattle may be their main reservoir.

@article{
 title = {Gut microbiota of frugo-folivorous sifakas across environments},
 type = {article},
 year = {2021},
 keywords = {Amplicon sequencing,Captivity,Folivory,Gut microbiome,Husbandry,Lemur,Madagascar,Metagenomic sequencing,Strepsirrhine primate},
 volume = {3},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {2e3a37e2-017e-3a23-b4a6-2ba0bb29e70d},
 created = {2025-10-30T12:26:01.034Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:07.655Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Captive animals, compared to their wild counterparts, generally harbor imbalanced gut microbiota owing, in part, to their altered diets. This imbalance is particularly striking for folivores that fundamentally rely on gut microbiota for digestion, yet rarely receive sufficient dietary fiber in captivity. We examine the critically endangered Coquerel’s sifaka (Propithecus coquereli), an anatomically specialized, rather than facultative, folivore that consumes a seasonal frugo-folivorous diet in the wild, but is provisioned predominantly with seasonal foliage and orchard vegetables in captivity. Using amplicon and metagenomic sequencing applied to fecal samples collected from two wild and one captive population (each comprising multiple groups), we clarify how dietary variation underlies the perturbational effect of captivity on the structure and function of this species’ gut microbiota. Results: The gut microbiota of wild sifakas varied by study population, most notably in community evenness and in the abundance of diet-associated microbes from Prevotellaeceae and Lachnospiraceae. Nevertheless, the differences among wild subjects were minor compared to those evident between wild and captive sifakas: Unusually, the consortia of captive sifakas were the most diverse, but lacked representation of endemic Bacteroidetes and metagenomic capacity for essential amino-acid biosynthesis. Instead, they were enriched for complex fiber metabolizers from the Firmicutes phylum, for archaeal methanogens, and for several metabolic pathways putatively linked to plant fiber and secondary compound metabolism. Conclusions: The relatively minor differences in gut microbial structure and function between wild sifaka populations likely reflect regional and/or temporal environmental variability, whereas the major differences observed in captive conspecifics, including the loss of endemic microbes, but gain in low-abundance taxa, likely reflect imbalanced or unstable consortia. Indeed, community perturbation may not necessarily entail decreased community diversity. Moreover, signatures of greater fiber degradation indicate that captive sifakas consume a more fibrous diet compared to their wild counterparts. These results do not mirror those typically reported for folivores and herbivores, suggesting that the direction and strength of captivity-induced ‘dysbiosis’ may not be universal across species with similar feeding strategies. We propose that tailored, species-specific dietary interventions in captivity, aimed at better approximating naturally foraged diets, could functionally ‘rewild’ gut microbiota and facilitate successful management of diverse species.},
 bibtype = {article},
 author = {Greene, Lydia K. and Blanco, Marina B. and Rambeloson, Elodi and Graubics, Karlis and Fanelli, Brian and Colwell, Rita R. and Drea, Christine M.},
 doi = {10.1186/S42523-021-00093-5},
 journal = {Animal Microbiome},
 number = {1}
}

Background: Captive animals, compared to their wild counterparts, generally harbor imbalanced gut microbiota owing, in part, to their altered diets. This imbalance is particularly striking for folivores that fundamentally rely on gut microbiota for digestion, yet rarely receive sufficient dietary fiber in captivity. We examine the critically endangered Coquerel’s sifaka (Propithecus coquereli), an anatomically specialized, rather than facultative, folivore that consumes a seasonal frugo-folivorous diet in the wild, but is provisioned predominantly with seasonal foliage and orchard vegetables in captivity. Using amplicon and metagenomic sequencing applied to fecal samples collected from two wild and one captive population (each comprising multiple groups), we clarify how dietary variation underlies the perturbational effect of captivity on the structure and function of this species’ gut microbiota. Results: The gut microbiota of wild sifakas varied by study population, most notably in community evenness and in the abundance of diet-associated microbes from Prevotellaeceae and Lachnospiraceae. Nevertheless, the differences among wild subjects were minor compared to those evident between wild and captive sifakas: Unusually, the consortia of captive sifakas were the most diverse, but lacked representation of endemic Bacteroidetes and metagenomic capacity for essential amino-acid biosynthesis. Instead, they were enriched for complex fiber metabolizers from the Firmicutes phylum, for archaeal methanogens, and for several metabolic pathways putatively linked to plant fiber and secondary compound metabolism. Conclusions: The relatively minor differences in gut microbial structure and function between wild sifaka populations likely reflect regional and/or temporal environmental variability, whereas the major differences observed in captive conspecifics, including the loss of endemic microbes, but gain in low-abundance taxa, likely reflect imbalanced or unstable consortia. Indeed, community perturbation may not necessarily entail decreased community diversity. Moreover, signatures of greater fiber degradation indicate that captive sifakas consume a more fibrous diet compared to their wild counterparts. These results do not mirror those typically reported for folivores and herbivores, suggesting that the direction and strength of captivity-induced ‘dysbiosis’ may not be universal across species with similar feeding strategies. We propose that tailored, species-specific dietary interventions in captivity, aimed at better approximating naturally foraged diets, could functionally ‘rewild’ gut microbiota and facilitate successful management of diverse species.

@article{
 title = {Metagenomic Sequencing and Quantitative Real-Time PCR for Fecal Pollution Assessment in an Urban Watershed},
 type = {article},
 year = {2021},
 keywords = {culture,fecal indicator bacteria,metagenomic analysis,microbial source tracking,quantitative real-time PCR,rainfall–runoff,whole metagenome sequence},
 volume = {3},
 month = {2},
 publisher = {Frontiers Media S.A.},
 day = {15},
 id = {cb87c0dd-df81-305d-bd8e-7544d1096575},
 created = {2025-10-30T12:26:01.800Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:11.548Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Microbial contamination of recreation waters is a major concern globally, with pollutants originating from many sources, including human and other animal wastes often introduced during storm events. Fecal contamination is traditionally monitored by employing culture methods targeting fecal indicator bacteria (FIB), namely E. coli and enterococci, which provides only limited information of a few microbial taxa and no information on their sources. Host-associated qPCR and metagenomic DNA sequencing are complementary methods for FIB monitoring that can provide enhanced understanding of microbial communities and sources of fecal pollution. Whole metagenome sequencing (WMS), quantitative real-time PCR (qPCR), and culture-based FIB tests were performed in an urban watershed before and after a rainfall event to determine the feasibility and application of employing a multi-assay approach for examining microbial content of ambient source waters. Cultivated E. coli and enterococci enumeration confirmed presence of fecal contamination in all samples exceeding local single sample recreational water quality thresholds (E. coli, 410 MPN/100 mL; enterococci, 107 MPN/100 mL) following a rainfall. Test results obtained with qPCR showed concentrations of E. coli, enterococci, and human-associated genetic markers increased after rainfall by 1.52-, 1.26-, and 1.11-fold log10 copies per 100 mL, respectively. Taxonomic analysis of the surface water microbiome and detection of antibiotic resistance genes, general FIB, and human-associated microorganisms were also employed. Results showed that fecal contamination from multiple sources (human, avian, dog, and ruminant), as well as FIB, enteric microorganisms, and antibiotic resistance genes increased demonstrably after a storm event. In summary, the addition of qPCR and WMS to traditional surrogate techniques may provide enhanced characterization and improved understanding of microbial pollution sources in ambient waters.},
 bibtype = {article},
 author = {Brumfield, Kyle D. and Cotruvo, Joseph A. and Shanks, Orin C. and Sivaganesan, Mano and Hey, Jessica and Hasan, Nur A. and Huq, Anwar and Colwell, Rita R. and Leddy, Menu B.},
 doi = {10.3389/FRWA.2021.626849},
 journal = {Frontiers in Water}
}

Microbial contamination of recreation waters is a major concern globally, with pollutants originating from many sources, including human and other animal wastes often introduced during storm events. Fecal contamination is traditionally monitored by employing culture methods targeting fecal indicator bacteria (FIB), namely E. coli and enterococci, which provides only limited information of a few microbial taxa and no information on their sources. Host-associated qPCR and metagenomic DNA sequencing are complementary methods for FIB monitoring that can provide enhanced understanding of microbial communities and sources of fecal pollution. Whole metagenome sequencing (WMS), quantitative real-time PCR (qPCR), and culture-based FIB tests were performed in an urban watershed before and after a rainfall event to determine the feasibility and application of employing a multi-assay approach for examining microbial content of ambient source waters. Cultivated E. coli and enterococci enumeration confirmed presence of fecal contamination in all samples exceeding local single sample recreational water quality thresholds (E. coli, 410 MPN/100 mL; enterococci, 107 MPN/100 mL) following a rainfall. Test results obtained with qPCR showed concentrations of E. coli, enterococci, and human-associated genetic markers increased after rainfall by 1.52-, 1.26-, and 1.11-fold log10 copies per 100 mL, respectively. Taxonomic analysis of the surface water microbiome and detection of antibiotic resistance genes, general FIB, and human-associated microorganisms were also employed. Results showed that fecal contamination from multiple sources (human, avian, dog, and ruminant), as well as FIB, enteric microorganisms, and antibiotic resistance genes increased demonstrably after a storm event. In summary, the addition of qPCR and WMS to traditional surrogate techniques may provide enhanced characterization and improved understanding of microbial pollution sources in ambient waters.

@article{
 title = {Aging-Induced Dysbiosis of Gut Microbiota as a Risk Factor for Increased Listeria monocytogenes Infection},
 type = {article},
 year = {2021},
 keywords = {Listeria monocytogenes,aging,dysbiosis,gut microbiota,inflammation,listeriosis,metagenomics},
 volume = {12},
 month = {4},
 publisher = {Frontiers Media S.A.},
 day = {28},
 id = {86569107-e97f-38db-9910-258e3d8389cd},
 created = {2025-10-30T12:26:01.891Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.891Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Invasive foodborne Listeria monocytogenes infection causes gastroenteritis, septicemia, meningitis, and chorioamnionitis, and is associated with high case-fatality rates in the elderly. It is unclear how aging alters gut microbiota, increases risk of listeriosis, and causes dysbiosis post-infection. We used a geriatric murine model of listeriosis as human surrogate of listeriosis for aging individuals to study the effect of aging and L. monocytogenes infection. Aging and listeriosis-induced perturbation of gut microbiota and disease severity were compared between young-adult and old mice. Young-adult and old mice were dosed intragastrically with L. monocytogenes. Fecal pellets were collected pre- and post-infection for microbiome analysis. Infected old mice had higher Listeria colonization in liver, spleen, and feces. Metagenomics analyses of fecal DNA-sequences showed increase in α-diversity as mice aged, and infection reduced its diversity. The relative abundance of major bacterial phylum like, Bacteroidetes and Firmicutes remained stable over aging or infection, while the Verrucomicrobia phylum was significantly reduced only in infected old mice. Old mice showed a marked reduction in Clostridaiceae and Lactobacillaceae bacteria even before infection when compared to uninfected young-adult mice. L. monocytogenes infection increased the abundance of Porphyromonadaceae and Prevotellaceae in young-adult mice, while members of the Ruminococcaceae and Lachnospiraceae family were significantly increased in old mice. The abundance of the genera Blautia and Alistipes were significantly reduced post-infection in young-adult and in old mice as compared to their uninfected counterparts. Butyrate producing, immune-modulating bacterial species, like Pseudoflavonifractor and Faecalibacterium were significantly increased only in old infected mice, correlating with increased intestinal inflammatory mRNA up-regulation from old mice tissue. Histologic analyses of gastric tissues showed extensive lesions in the Listeria-infected old mice, more so in the non-glandular region and fundus than in the pylorus. Commensal species like Lactobacillus, Clostridiales, and Akkermansia were only abundant in infected young-adult mice but their abundance diminished in the infected old mice. Listeriosis in old mice enhances the abundance of butyrate-producing inflammatory members of the Ruminococcaceae/Lachnospiraceae bacteria while reducing/eliminating beneficial commensals in the gut. Results of this study indicate that, aging may affect the composition of gut microbiota and increase the risk of invasive L. monocytogenes infection.},
 bibtype = {article},
 author = {Alam, Mohammad S. and Gangiredla, Jayanthi and Hasan, Nur A. and Barnaba, Tammy and Tartera, Carmen},
 doi = {10.3389/FIMMU.2021.672353},
 journal = {Frontiers in Immunology}
}

Invasive foodborne Listeria monocytogenes infection causes gastroenteritis, septicemia, meningitis, and chorioamnionitis, and is associated with high case-fatality rates in the elderly. It is unclear how aging alters gut microbiota, increases risk of listeriosis, and causes dysbiosis post-infection. We used a geriatric murine model of listeriosis as human surrogate of listeriosis for aging individuals to study the effect of aging and L. monocytogenes infection. Aging and listeriosis-induced perturbation of gut microbiota and disease severity were compared between young-adult and old mice. Young-adult and old mice were dosed intragastrically with L. monocytogenes. Fecal pellets were collected pre- and post-infection for microbiome analysis. Infected old mice had higher Listeria colonization in liver, spleen, and feces. Metagenomics analyses of fecal DNA-sequences showed increase in α-diversity as mice aged, and infection reduced its diversity. The relative abundance of major bacterial phylum like, Bacteroidetes and Firmicutes remained stable over aging or infection, while the Verrucomicrobia phylum was significantly reduced only in infected old mice. Old mice showed a marked reduction in Clostridaiceae and Lactobacillaceae bacteria even before infection when compared to uninfected young-adult mice. L. monocytogenes infection increased the abundance of Porphyromonadaceae and Prevotellaceae in young-adult mice, while members of the Ruminococcaceae and Lachnospiraceae family were significantly increased in old mice. The abundance of the genera Blautia and Alistipes were significantly reduced post-infection in young-adult and in old mice as compared to their uninfected counterparts. Butyrate producing, immune-modulating bacterial species, like Pseudoflavonifractor and Faecalibacterium were significantly increased only in old infected mice, correlating with increased intestinal inflammatory mRNA up-regulation from old mice tissue. Histologic analyses of gastric tissues showed extensive lesions in the Listeria-infected old mice, more so in the non-glandular region and fundus than in the pylorus. Commensal species like Lactobacillus, Clostridiales, and Akkermansia were only abundant in infected young-adult mice but their abundance diminished in the infected old mice. Listeriosis in old mice enhances the abundance of butyrate-producing inflammatory members of the Ruminococcaceae/Lachnospiraceae bacteria while reducing/eliminating beneficial commensals in the gut. Results of this study indicate that, aging may affect the composition of gut microbiota and increase the risk of invasive L. monocytogenes infection.

@article{
 title = {Diet, obesity, and the gut microbiome as determinants modulating metabolic outcomes in a non-human primate model},
 type = {article},
 year = {2021},
 keywords = {Body fat composition,Eubacterium siraeum,Metabolomics,Metagenomic sequencing,Prevotella copri,Uremic toxins,Urinary carnitine metabolites,Western and Mediterranean diet},
 volume = {9},
 month = {12},
 publisher = {BioMed Central Ltd},
 day = {1},
 id = {1dfedca1-ad10-371e-b438-ba440938a0a8},
 created = {2025-10-30T12:26:02.112Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:11.182Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Abstract: Background: The objective of this study was to increase understanding of the complex interactions between diet, obesity, and the gut microbiome of adult female non-human primates (NHPs). Subjects consumed either a Western (n=15) or Mediterranean (n=14) diet designed to represent human dietary patterns for 31 months. Body composition was determined using CT, fecal samples were collected, and shotgun metagenomic sequencing was performed. Gut microbiome results were grouped by diet and adiposity. Results: Diet was the main contributor to gut microbiome bacterial diversity. Adiposity within each diet was associated with subtle shifts in the proportional abundance of several taxa. Mediterranean diet-fed NHPs with lower body fat had a greater proportion of Lactobacillus animalis than their higher body fat counterparts. Higher body fat Western diet-fed NHPs had more Ruminococcus champaneliensis and less Bacteroides uniformis than their low body fat counterparts. Western diet-fed NHPs had significantly higher levels of Prevotella copri than Mediterranean diet NHPs. Western diet-fed subjects were stratified by P. copri abundance (P. copriHIGH versus P. copriLOW), which was not associated with adiposity. Overall, Western diet-fed animals in the P. copriHIGH group showed greater proportional abundance of B. ovatus, B. faecis, P. stercorea, P. brevis, and Faecalibacterium prausnitzii than those in the Western P. copriLOW group. Western diet P. copriLOW subjects had a greater proportion of Eubacterium siraeum. E. siraeum negatively correlated with P. copri proportional abundance regardless of dietary consumption. In the Western diet group, Shannon diversity was significantly higher in P. copriLOW when compared to P. copriHIGH subjects. Furthermore, gut E. siraeum abundance positively correlated with HDL plasma cholesterol indicating that those in the P. copriLOW population may represent a more metabolically healthy population. Untargeted metabolomics on urine and plasma from Western diet-fed P. copriHIGH and P. copriLOW subjects suggest early kidney dysfunction in Western diet-fed P. copriHIGH subjects. Conclusions: In summary, the data indicate diet to be the major influencer of gut bacterial diversity. However, diet and adiposity must be considered together when analyzing changes in abundance of specific bacterial taxa. Interestingly, P. copri appears to mediate metabolic dysfunction in Western diet-fed NHPs. [MediaObject not available: see fulltext.]},
 bibtype = {article},
 author = {Newman, Tiffany M. and Shively, Carol A. and Register, Thomas C. and Appt, Susan E. and Yadav, Hariom and Colwell, Rita R. and Fanelli, Brian and Dadlani, Manoj and Graubics, Karlis and Nguyen, Uyen Thao and Ramamoorthy, Sivapriya and Uberseder, Beth and Clear, Kenysha Y.J. and Wilson, Adam S. and Reeves, Kimberly D. and Chappell, Mark C. and Tooze, Janet A. and Cook, Katherine L.},
 doi = {10.1186/S40168-021-01069-Y},
 journal = {Microbiome},
 number = {1}
}

Abstract: Background: The objective of this study was to increase understanding of the complex interactions between diet, obesity, and the gut microbiome of adult female non-human primates (NHPs). Subjects consumed either a Western (n=15) or Mediterranean (n=14) diet designed to represent human dietary patterns for 31 months. Body composition was determined using CT, fecal samples were collected, and shotgun metagenomic sequencing was performed. Gut microbiome results were grouped by diet and adiposity. Results: Diet was the main contributor to gut microbiome bacterial diversity. Adiposity within each diet was associated with subtle shifts in the proportional abundance of several taxa. Mediterranean diet-fed NHPs with lower body fat had a greater proportion of Lactobacillus animalis than their higher body fat counterparts. Higher body fat Western diet-fed NHPs had more Ruminococcus champaneliensis and less Bacteroides uniformis than their low body fat counterparts. Western diet-fed NHPs had significantly higher levels of Prevotella copri than Mediterranean diet NHPs. Western diet-fed subjects were stratified by P. copri abundance (P. copriHIGH versus P. copriLOW), which was not associated with adiposity. Overall, Western diet-fed animals in the P. copriHIGH group showed greater proportional abundance of B. ovatus, B. faecis, P. stercorea, P. brevis, and Faecalibacterium prausnitzii than those in the Western P. copriLOW group. Western diet P. copriLOW subjects had a greater proportion of Eubacterium siraeum. E. siraeum negatively correlated with P. copri proportional abundance regardless of dietary consumption. In the Western diet group, Shannon diversity was significantly higher in P. copriLOW when compared to P. copriHIGH subjects. Furthermore, gut E. siraeum abundance positively correlated with HDL plasma cholesterol indicating that those in the P. copriLOW population may represent a more metabolically healthy population. Untargeted metabolomics on urine and plasma from Western diet-fed P. copriHIGH and P. copriLOW subjects suggest early kidney dysfunction in Western diet-fed P. copriHIGH subjects. Conclusions: In summary, the data indicate diet to be the major influencer of gut bacterial diversity. However, diet and adiposity must be considered together when analyzing changes in abundance of specific bacterial taxa. Interestingly, P. copri appears to mediate metabolic dysfunction in Western diet-fed NHPs. [MediaObject not available: see fulltext.]

@article{
 title = {Defensive strategies of Norway spruce and Kurile larch heartwood elucidated on the micron-level},
 type = {article},
 year = {2021},
 volume = {11},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {d769af1c-ca7e-32a5-9018-291650fb230a},
 created = {2025-10-30T12:28:33.413Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:38.781Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {To decarbonize the building sector, the use of durable wood materials must be increased. Inspiration for environmentally benign wood protection systems is sought in durable tree species depositing phenolic extractives in their heartwood. Based on the hypothesis that the micro-distribution of extractives influences durability, we compared the natural impregnation patterns of non-durable, but readily available Norway spruce to more durable Kurile larch by mapping the distribution of heartwood extractives with Confocal Raman Imaging and multivariate data decomposition. Phenolics of both species were associated with hydrophobic oleoresin, likely facilitating diffusion through the tissue. They accumulated preferentially in lignin-rich sub-compartments of the cell wall. Yet, the distribution of extractives was found not to be the same. The middle lamellae contained flavonoids in larch and aromatic waxes in spruce, which was also found in rays and epithelial cells. Spruce-lignans were tentatively identified in all cell types, while larch-flavonoids were not present in resin channels, hinting at a different origin of synthesis. Larch-oleoresin without flavonoids was only found in lumina, indicating that the presence of phenolics in the mixture influences the final destination. Together our findings suggest, that spruce heartwood-defense focuses on water regulation, while the more efficient larch strategy is based on antioxidants.},
 bibtype = {article},
 author = {Füchtner, Sophie and Piqueras, Sara and Thygesen, Lisbeth Garbrecht},
 doi = {10.1038/s41598-021-01590-y},
 journal = {Scientific Reports},
 number = {1}
}

To decarbonize the building sector, the use of durable wood materials must be increased. Inspiration for environmentally benign wood protection systems is sought in durable tree species depositing phenolic extractives in their heartwood. Based on the hypothesis that the micro-distribution of extractives influences durability, we compared the natural impregnation patterns of non-durable, but readily available Norway spruce to more durable Kurile larch by mapping the distribution of heartwood extractives with Confocal Raman Imaging and multivariate data decomposition. Phenolics of both species were associated with hydrophobic oleoresin, likely facilitating diffusion through the tissue. They accumulated preferentially in lignin-rich sub-compartments of the cell wall. Yet, the distribution of extractives was found not to be the same. The middle lamellae contained flavonoids in larch and aromatic waxes in spruce, which was also found in rays and epithelial cells. Spruce-lignans were tentatively identified in all cell types, while larch-flavonoids were not present in resin channels, hinting at a different origin of synthesis. Larch-oleoresin without flavonoids was only found in lumina, indicating that the presence of phenolics in the mixture influences the final destination. Together our findings suggest, that spruce heartwood-defense focuses on water regulation, while the more efficient larch strategy is based on antioxidants.

@article{
 title = {The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome.},
 type = {article},
 year = {2021},
 keywords = {2′-O-fucosyllactose,antibacterial response,gut microenvironment,human milk oligosaccharides,irritable bowel syndrome,lacto-N-neotetraose,metabolomics,microbiota},
 volume = {13},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/34836092,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8622683},
 month = {10},
 publisher = {MDPI},
 day = {27},
 id = {95e286b6-3ee5-35d8-93e6-e520622e982e},
 created = {2025-10-30T12:28:33.421Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:29:03.633Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {BACKGROUND Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2'-O-fucosyllactose and lacto-N-neotetraose (2'FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. METHODS Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2'FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. RESULTS Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2'FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2'FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. CONCLUSION Supplementation with 2'FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2'FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.},
 bibtype = {article},
 author = {Iribarren, Cristina and Magnusson, Maria K and Vigsnæs, Louise K and Aziz, Imran and Amundsen, Ingvild Dybdrodt and Šuligoj, Tanja and Juge, Nathalie and Patel, Piyush and Sapnara, Maria and Johnsen, Lea and Sørensen, Nikolaj and Sundin, Johanna and Törnblom, Hans and Simrén, Magnus and Öhman, Lena},
 doi = {10.3390/nu13113836},
 journal = {Nutrients},
 number = {11}
}

BACKGROUND Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2'-O-fucosyllactose and lacto-N-neotetraose (2'FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. METHODS Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2'FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. RESULTS Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2'FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2'FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. CONCLUSION Supplementation with 2'FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2'FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.

@article{
 title = {Host Stress Signals Stimulate Pneumococcal Transition from Colonization to Dissemination into the Lungs},
 type = {article},
 year = {2021},
 keywords = {Bacterial infection,Streptococcus pneumoniae,Stress hormone,Two-component regulatory system,Virulence},
 volume = {12},
 month = {12},
 publisher = {American Society for Microbiology},
 day = {1},
 id = {fb92075c-ed9e-32f7-92e5-5202681983ec},
 created = {2025-10-30T12:28:33.450Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:33.450Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Streptococcus pneumoniae is an asymptomatic colonizer of the nasopharynx, but it is also one of the most important bacterial pathogens of humans, causing a wide range of mild to life-threatening diseases. The basis of the pneumococcal transition from a commensal to a parasitic lifestyle is not fully understood. We hypothesize that exposure to host catecholamine stress hormones is important for this transition. In this study, we demonstrated that pneumococci preexposed to a hormone released during stress, norepinephrine (NE), have an increased capacity to translocate from the nasopharynx into the lungs compared to untreated pneumococci. Examination of NE-treated pneumococci revealed major alterations in metabolic profiles, cell associations, capsule synthesis, and cell size. By systemically mutating all 12 two-component and 1 orphan regulatory systems, we also identified a unique genetic regulatory circuit involved in pneumococcal recognition and responsiveness to human stress hormones. IMPORTANCE Microbes acquire unique lifestyles under different environmental conditions. Although this is a widespread occurrence, our knowledge of the importance of various host signals and their impact on microbial behavior is not clear despite the therapeutic value of this knowledge. We discovered that catecholamine stress hormones are the host signals that trigger the passage of Streptococcus pneumoniae from a commensal to a parasitic state. We identify that stress hormone treatment of this microbe leads to reductions in cell size and capsule synthesis and renders it more able to migrate from the nasopharynx into the lungs in a mouse model of infection. The microbe requires the TCS09 protein for the recognition and processing of stress hormone signals. Our work has particular clinical significance as catecholamines are abundant in upper respiratory fluids as well as being administered therapeutically to reduce inflammation in ventilated patients, which may explain why intubation in the critically ill is a recognized risk factor for the development of pneumococcal pneumonia.},
 bibtype = {article},
 author = {Alghofaili, Fayez and Najmuldeen, Hastyar and Kareem, Banaz O. and Shlla, Bushra and Fernandes, Vitor E. and Danielsen, Morten and Ketley, Julian M. and Freestone, Primrose and Yesilkaya, Hasan},
 doi = {10.1128/mBio.02569-21},
 journal = {mBio},
 number = {6}
}

Streptococcus pneumoniae is an asymptomatic colonizer of the nasopharynx, but it is also one of the most important bacterial pathogens of humans, causing a wide range of mild to life-threatening diseases. The basis of the pneumococcal transition from a commensal to a parasitic lifestyle is not fully understood. We hypothesize that exposure to host catecholamine stress hormones is important for this transition. In this study, we demonstrated that pneumococci preexposed to a hormone released during stress, norepinephrine (NE), have an increased capacity to translocate from the nasopharynx into the lungs compared to untreated pneumococci. Examination of NE-treated pneumococci revealed major alterations in metabolic profiles, cell associations, capsule synthesis, and cell size. By systemically mutating all 12 two-component and 1 orphan regulatory systems, we also identified a unique genetic regulatory circuit involved in pneumococcal recognition and responsiveness to human stress hormones. IMPORTANCE Microbes acquire unique lifestyles under different environmental conditions. Although this is a widespread occurrence, our knowledge of the importance of various host signals and their impact on microbial behavior is not clear despite the therapeutic value of this knowledge. We discovered that catecholamine stress hormones are the host signals that trigger the passage of Streptococcus pneumoniae from a commensal to a parasitic state. We identify that stress hormone treatment of this microbe leads to reductions in cell size and capsule synthesis and renders it more able to migrate from the nasopharynx into the lungs in a mouse model of infection. The microbe requires the TCS09 protein for the recognition and processing of stress hormone signals. Our work has particular clinical significance as catecholamines are abundant in upper respiratory fluids as well as being administered therapeutically to reduce inflammation in ventilated patients, which may explain why intubation in the critically ill is a recognized risk factor for the development of pneumococcal pneumonia.

@article{
 title = {Publisher Correction: Inhibition of succinate dehydrogenase activity impairs human T cell activation and function (Scientific Reports, (2021), 11, 1, (1458), 10.1038/s41598-020-80933-7)},
 type = {article},
 year = {2021},
 volume = {11},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {b09fd68c-df44-3a24-80b3-039780376466},
 created = {2025-10-30T12:28:33.457Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:33.457Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The Author Contributions section in this Article is incorrect. “A.W.-O. and C.N. designed the research. C.N. performed experiments, analysed and interpreted the data, made the figures, and wrote the original draft of the paper. A.W.-O. performed microarray analysis. K.D. and M.D. performed metabolome analysis. C.N., A.W.-O., K.D., S.L.F, A.S.Ø.G., T.B.B., M.G., M.D., C.M.B., C.G., T.L., N.Ø. and A.W. reviewed and edited the manuscript. A.W.-O. acquired the funding.”},
 bibtype = {article},
 author = {Nastasi, Claudia and Willerlev-Olsen, Andreas and Dalhoff, Kristoffer and Ford, Shayne L. and Gadsbøll, Anne Sofie Østergaard and Buus, Terkild Brink and Gluud, Maria and Danielsen, Morten and Litman, Thomas and Bonefeld, Charlotte Mennè and Geisler, Carsten and Ødum, Niels and Woetmann, Anders},
 doi = {10.1038/s41598-021-88184-w},
 journal = {Scientific Reports},
 number = {1}
}

The Author Contributions section in this Article is incorrect. “A.W.-O. and C.N. designed the research. C.N. performed experiments, analysed and interpreted the data, made the figures, and wrote the original draft of the paper. A.W.-O. performed microarray analysis. K.D. and M.D. performed metabolome analysis. C.N., A.W.-O., K.D., S.L.F, A.S.Ø.G., T.B.B., M.G., M.D., C.M.B., C.G., T.L., N.Ø. and A.W. reviewed and edited the manuscript. A.W.-O. acquired the funding.”

@article{
 title = {Inhibition of succinate dehydrogenase activity impairs human T cell activation and function},
 type = {article},
 year = {2021},
 volume = {11},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {61efa6f5-60fe-3bdf-9a38-1076fa0aa867},
 created = {2025-10-30T12:28:33.458Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:37.645Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {T cell activation is intimately linked to metabolism, as distinct metabolic requirements support the functional and phenotypical differences between quiescent and activated T cells. Metabolic transition from mitochondrial oxidative phosphorylation to aerobic glycolysis is crucial for a proper T cell activation. However, the role of tricarboxylic acid cycle (TCA), and in particular succinate dehydrogenase (SDH) in activated T cells needs further elucidation. Here we show that inhibition of SDH during activation of T cells results in strong impairment of proliferation, expression of activation markers, and production of key inflammatory cytokines, despite a concomitant increase in glycolytic metabolic activity. Similar effect of SDH inhibition were demonstrated in pre-activated T cell. Interestingly, itaconic acid, an endogenous SDH inhibitor released from activated macrophages and dendritic cells, had no immunomodulator effect. Taken together, our findings demonstrate that SDH enzyme fitness is critical for mounting and maintaining appropriate activation and function of human T cells.},
 bibtype = {article},
 author = {Nastasi, Claudia and Willerlev-Olsen, Andreas and Dalhoff, Kristoffer and Ford, Shayne L. and Gadsbøll, Anne Sofie Østergaard and Buus, Terkild Brink and Gluud, Maria and Danielsen, Morten and Litman, Thomas and Bonefeld, Charlotte Mennè and Geisler, Carsten and Ødum, Niels and Woetmann, Anders},
 doi = {10.1038/s41598-020-80933-7},
 journal = {Scientific Reports},
 number = {1}
}

T cell activation is intimately linked to metabolism, as distinct metabolic requirements support the functional and phenotypical differences between quiescent and activated T cells. Metabolic transition from mitochondrial oxidative phosphorylation to aerobic glycolysis is crucial for a proper T cell activation. However, the role of tricarboxylic acid cycle (TCA), and in particular succinate dehydrogenase (SDH) in activated T cells needs further elucidation. Here we show that inhibition of SDH during activation of T cells results in strong impairment of proliferation, expression of activation markers, and production of key inflammatory cytokines, despite a concomitant increase in glycolytic metabolic activity. Similar effect of SDH inhibition were demonstrated in pre-activated T cell. Interestingly, itaconic acid, an endogenous SDH inhibitor released from activated macrophages and dendritic cells, had no immunomodulator effect. Taken together, our findings demonstrate that SDH enzyme fitness is critical for mounting and maintaining appropriate activation and function of human T cells.

@article{
 title = {Antiviral activity of bacterial TIR domains via immune signalling molecules},
 type = {article},
 year = {2021},
 pages = {116-120},
 volume = {600},
 month = {12},
 publisher = {Nature Research},
 day = {2},
 id = {ddc291e6-33be-35af-9c3d-3281d3534a1b},
 created = {2025-10-30T12:28:33.488Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:33.488Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems1,2. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule that is a variant of cyclic ADP-ribose3,4. This molecule is hypothesized to mediate plant cell death through a pathway that has yet to be resolved5. TIR domains have also been shown to be involved in a bacterial anti-phage defence system called Thoeris6, but the mechanism of Thoeris defence remained unknown. Here we show that phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose. This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death. We also show that, similar to eukaryotic innate immune systems, bacterial TIR-domain proteins determine the immunological specificity to the invading pathogen. Our results describe an antiviral signalling pathway in bacteria, and suggest that the generation of intracellular signalling molecules is an ancient immunological function of TIR domains that is conserved in both plant and bacterial immunity.},
 bibtype = {article},
 author = {Ofir, Gal and Herbst, Ehud and Baroz, Maya and Cohen, Daniel and Millman, Adi and Doron, Shany and Tal, Nitzan and Malheiro, Daniel B.A. and Malitsky, Sergey and Amitai, Gil and Sorek, Rotem},
 doi = {10.1038/s41586-021-04098-7},
 journal = {Nature},
 number = {7887}
}

The Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems1,2. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule that is a variant of cyclic ADP-ribose3,4. This molecule is hypothesized to mediate plant cell death through a pathway that has yet to be resolved5. TIR domains have also been shown to be involved in a bacterial anti-phage defence system called Thoeris6, but the mechanism of Thoeris defence remained unknown. Here we show that phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose. This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death. We also show that, similar to eukaryotic innate immune systems, bacterial TIR-domain proteins determine the immunological specificity to the invading pathogen. Our results describe an antiviral signalling pathway in bacteria, and suggest that the generation of intracellular signalling molecules is an ancient immunological function of TIR domains that is conserved in both plant and bacterial immunity.

@article{
 title = {Assessing Population Diversity of Brettanomyces Yeast Species and Identification of Strains for Brewing Applications},
 type = {article},
 year = {2020},
 keywords = {4-ethylguaiacol,Dekkera bruxellensis,beta-glucosidase,brewing fermentation,genomics,high-throughput screening,maltose assimilation,phenolic off-flavor},
 pages = {495404},
 volume = {11},
 websites = {www.frontiersin.org},
 month = {4},
 publisher = {Frontiers Media S.A.},
 day = {9},
 id = {a549cd82-02cd-329e-9797-234410706e33},
 created = {2025-07-07T13:25:25.208Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:11.389Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Brettanomyces yeasts have gained popularity in many sectors of the biotechnological industry, specifically in the field of beer production, but also in wine and ethanol production. Their unique properties enable Brettanomyces to outcompete conventional brewer’s yeast in industrially relevant traits such as production of ethanol and pleasant flavors. Recent advances in next-generation sequencing (NGS) and high-throughput screening techniques have facilitated large population studies allowing the selection of appropriate yeast strains with improved traits. In order to get a better understanding of Brettanomyces species and its potential for beer production, we sequenced the whole genome of 84 strains, which we make available to the scientific community and carried out several in vitro assays for brewing-relevant properties. The collection includes isolates from different substrates and geographical origin. Additionally, we have included two of the oldest Carlsberg Research Laboratory isolates. In this study, we reveal the phylogenetic pattern of Brettanomyces species by comparing the predicted proteomes of each strain. Furthermore, we show that the Brettanomyces collection is well described using similarity in genomic organization, and that there is a direct correlation between genomic background and phenotypic characteristics. Particularly, genomic patterns affecting flavor production, maltose assimilation, beta-glucosidase activity, and phenolic off-flavor (POF) production are reported. This knowledge yields new insights into Brettanomyces population survival strategies, artificial selection pressure, and loss of carbon assimilation traits. On a species-specific level, we have identified for the first time a POF negative Brettanomyces anomalus strain, without the main spoilage character of Brettanomyces species. This strain (CRL-90) has lost DaPAD1, making it incapable of converting ferulic acid to 4-ethylguaiacol (4-EG) and 4-ethylphenol (4-EP). This loss of function makes CRL-90 a good candidate for the production of characteristic Brettanomyces flavors in beverages, without the contaminant increase in POF. Overall, this study displays the potential of exploring Brettanomyces yeast species biodiversity to find strains with relevant properties applicable to the brewing industry.},
 bibtype = {article},
 author = {Colomer, Marc Serra and Chailyan, Anna and Fennessy, Ross T. and Olsson, Kim Friis and Johnsen, Lea and Solodovnikova, Natalia and Forster, Jochen},
 doi = {10.3389/FMICB.2020.00637/BIBTEX},
 journal = {Frontiers in Microbiology}
}

Brettanomyces yeasts have gained popularity in many sectors of the biotechnological industry, specifically in the field of beer production, but also in wine and ethanol production. Their unique properties enable Brettanomyces to outcompete conventional brewer’s yeast in industrially relevant traits such as production of ethanol and pleasant flavors. Recent advances in next-generation sequencing (NGS) and high-throughput screening techniques have facilitated large population studies allowing the selection of appropriate yeast strains with improved traits. In order to get a better understanding of Brettanomyces species and its potential for beer production, we sequenced the whole genome of 84 strains, which we make available to the scientific community and carried out several in vitro assays for brewing-relevant properties. The collection includes isolates from different substrates and geographical origin. Additionally, we have included two of the oldest Carlsberg Research Laboratory isolates. In this study, we reveal the phylogenetic pattern of Brettanomyces species by comparing the predicted proteomes of each strain. Furthermore, we show that the Brettanomyces collection is well described using similarity in genomic organization, and that there is a direct correlation between genomic background and phenotypic characteristics. Particularly, genomic patterns affecting flavor production, maltose assimilation, beta-glucosidase activity, and phenolic off-flavor (POF) production are reported. This knowledge yields new insights into Brettanomyces population survival strategies, artificial selection pressure, and loss of carbon assimilation traits. On a species-specific level, we have identified for the first time a POF negative Brettanomyces anomalus strain, without the main spoilage character of Brettanomyces species. This strain (CRL-90) has lost DaPAD1, making it incapable of converting ferulic acid to 4-ethylguaiacol (4-EG) and 4-ethylphenol (4-EP). This loss of function makes CRL-90 a good candidate for the production of characteristic Brettanomyces flavors in beverages, without the contaminant increase in POF. Overall, this study displays the potential of exploring Brettanomyces yeast species biodiversity to find strains with relevant properties applicable to the brewing industry.

@article{
 title = {Comparative proteomic analysis of SLC13A5 knockdown reveals elevated ketogenesis and enhanced cellular toxic response to chemotherapeutic agents in HepG2 cells},
 type = {article},
 year = {2020},
 keywords = {Antineoplastic Agents / pharmacology*,Cell Survival / drug effects,Extramural,Gene Expression Regulation / drug effects*,Gene Knockdown Techniques,Hep G2 Cells,Hongbing Wang,Humans,Ketones / metabolism*,MEDLINE,N.I.H.,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,PMC7398853,PubMed Abstract,Research Support,Symporters / genetics,Symporters / metabolism*,Tao Hu,Weiliang Huang,doi:10.1016/j.taap.2020.115117,pmid:32634519},
 volume = {402},
 websites = {https://pubmed.ncbi.nlm.nih.gov/32634519/},
 month = {9},
 publisher = {Toxicol Appl Pharmacol},
 day = {1},
 id = {13bcf20b-3b99-3076-8101-0f7006b95363},
 created = {2025-07-07T13:25:25.548Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:25.548Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Solute carrier family 13 member 5 (SLC13A5) is an uptake transporter mainly expressed in the liver and transports citrate from blood circulation into hepatocytes. Accumulating evidence suggests that SLC13A5 is involved in hepatic lipogenesis, cell proliferation, epilepsy, and bone development in mammals. However, the molecular mechanisms behind SLC13A5-mediated physiological/pathophysiological changes are largely unknown. In this regard, we conducted a differential proteome analysis in HepG2 and SLC13A5-knockdown (KD) HepG2 cells. A total of 3826 proteins were quantified and 330 proteins showed significant alterations (fold change ≥1.5; p < .05) in the knockdown cells. Gene ontology enrichment analysis reveals that 38 biological processes were significantly changed, with ketone body biosynthetic process showing the most significant upregulation following SLC13A5-KD. Catalytic activity and binding activity were the top two molecular functions associated with differentially expressed proteins, while HMG-CoA lyase activity showed the highest fold enrichment. Further ingenuity pathway analysis predicted 40 canonical pathways and 28 upstream regulators (p < .01), of which most were associated with metabolism, cell proliferation, and stress response. In line with these findings, functional validation demonstrated increased levels of two key ketone bodies, acetoacetate and β-hydroxybutyrate, in the SLC13A5-KD cells. Additional experiments showed that SLC13A5-KD sensitizes HepG2 cells to cellular stress caused by a number of chemotherapeutic agents. Together, our findings demonstrate that knockdown of SLC13A5 promotes hepatic ketogenesis and enhances cellular stress response in HepG2 cells, suggesting a potential role of this transporter in metabolic disorders and liver cancer.},
 bibtype = {article},
 author = {Hu, Tao and Huang, Weiliang and Li, Zhihui and Kane, Maureen A. and Zhang, Lei and Huang, Shiew Mei and Wang, Hongbing},
 doi = {10.1016/J.TAAP.2020.115117},
 journal = {Toxicology and applied pharmacology}
}

Solute carrier family 13 member 5 (SLC13A5) is an uptake transporter mainly expressed in the liver and transports citrate from blood circulation into hepatocytes. Accumulating evidence suggests that SLC13A5 is involved in hepatic lipogenesis, cell proliferation, epilepsy, and bone development in mammals. However, the molecular mechanisms behind SLC13A5-mediated physiological/pathophysiological changes are largely unknown. In this regard, we conducted a differential proteome analysis in HepG2 and SLC13A5-knockdown (KD) HepG2 cells. A total of 3826 proteins were quantified and 330 proteins showed significant alterations (fold change ≥1.5; p < .05) in the knockdown cells. Gene ontology enrichment analysis reveals that 38 biological processes were significantly changed, with ketone body biosynthetic process showing the most significant upregulation following SLC13A5-KD. Catalytic activity and binding activity were the top two molecular functions associated with differentially expressed proteins, while HMG-CoA lyase activity showed the highest fold enrichment. Further ingenuity pathway analysis predicted 40 canonical pathways and 28 upstream regulators (p < .01), of which most were associated with metabolism, cell proliferation, and stress response. In line with these findings, functional validation demonstrated increased levels of two key ketone bodies, acetoacetate and β-hydroxybutyrate, in the SLC13A5-KD cells. Additional experiments showed that SLC13A5-KD sensitizes HepG2 cells to cellular stress caused by a number of chemotherapeutic agents. Together, our findings demonstrate that knockdown of SLC13A5 promotes hepatic ketogenesis and enhances cellular stress response in HepG2 cells, suggesting a potential role of this transporter in metabolic disorders and liver cancer.

@article{
 title = {Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse},
 type = {article},
 year = {2020},
 keywords = {MCF,SCFA},
 pages = {1-20},
 volume = {8},
 websites = {https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-020-00846-5},
 month = {5},
 publisher = {BioMed Central Ltd.},
 day = {18},
 id = {b051030c-1e77-3199-b951-131100c32425},
 created = {2025-07-07T13:25:25.913Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:11.855Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Mounting evidence suggests a role for the gut microbiota in modulating brain physiology and behaviour, through bi-directional communication, along the gut-brain axis. As such, the gut microbiota represents a potential therapeutic target for influencing centrally mediated events and host behaviour. It is thus notable that the fermented milk beverage kefir has recently been shown to modulate the composition of the gut microbiota in mice. It is unclear whether kefirs have differential effects on microbiota-gut-brain axis and whether they can modulate host behaviour per se. Methods: To address this, two distinct kefirs (Fr1 and UK4), or unfermented milk control, were administered to mice that underwent a battery of tests to characterise their behavioural phenotype. In addition, shotgun metagenomic sequencing of ileal, caecal and faecal matter was performed, as was faecal metabolome analysis. Finally, systemic immunity measures and gut serotonin levels were assessed. Statistical analyses were performed by ANOVA followed by Dunnett's post hoc test or Kruskal-Wallis test followed by Mann-Whitney U test. Results: Fr1 ameliorated the stress-induced decrease in serotonergic signalling in the colon and reward-seeking behaviour in the saccharin preference test. On the other hand, UK4 decreased repetitive behaviour and ameliorated stress-induced deficits in reward-seeking behaviour. Furthermore, UK4 increased fear-dependent contextual memory, yet decreased milk gavage-induced improvements in long-term spatial learning. In the peripheral immune system, UK4 increased the prevalence of Treg cells and interleukin 10 levels, whereas Fr1 ameliorated the milk gavage stress-induced elevation in neutrophil levels and CXCL1 levels. Analysis of the gut microbiota revealed that both kefirs significantly changed the composition and functional capacity of the host microbiota, where specific bacterial species were changed in a kefir-dependent manner. Furthermore, both kefirs increased the capacity of the gut microbiota to produce GABA, which was linked to an increased prevalence in Lactobacillus reuteri. Conclusions: Altogether, these data show that kefir can signal through the microbiota-gut-immune-brain axis and modulate host behaviour. In addition, different kefirs may direct the microbiota toward distinct immunological and behavioural modulatory effects. These results indicate that kefir can positively modulate specific aspects of the microbiota-gut-brain axis and support the broadening of the definition of psychobiotic to include kefir fermented foods. [MediaObject not available: see fulltext.]},
 bibtype = {article},
 author = {Van De Wouw, Marcel and Walsh, Aaron M. and Crispie, Fiona and Van Leuven, Lucas and Lyte, Joshua M. and Boehme, Marcus and Clarke, Gerard and Dinan, Timothy G. and Cotter, Paul D. and Cryan, John F.},
 doi = {10.1186/S40168-020-00846-5/FIGURES/9},
 journal = {Microbiome},
 number = {1}
}

Background: Mounting evidence suggests a role for the gut microbiota in modulating brain physiology and behaviour, through bi-directional communication, along the gut-brain axis. As such, the gut microbiota represents a potential therapeutic target for influencing centrally mediated events and host behaviour. It is thus notable that the fermented milk beverage kefir has recently been shown to modulate the composition of the gut microbiota in mice. It is unclear whether kefirs have differential effects on microbiota-gut-brain axis and whether they can modulate host behaviour per se. Methods: To address this, two distinct kefirs (Fr1 and UK4), or unfermented milk control, were administered to mice that underwent a battery of tests to characterise their behavioural phenotype. In addition, shotgun metagenomic sequencing of ileal, caecal and faecal matter was performed, as was faecal metabolome analysis. Finally, systemic immunity measures and gut serotonin levels were assessed. Statistical analyses were performed by ANOVA followed by Dunnett's post hoc test or Kruskal-Wallis test followed by Mann-Whitney U test. Results: Fr1 ameliorated the stress-induced decrease in serotonergic signalling in the colon and reward-seeking behaviour in the saccharin preference test. On the other hand, UK4 decreased repetitive behaviour and ameliorated stress-induced deficits in reward-seeking behaviour. Furthermore, UK4 increased fear-dependent contextual memory, yet decreased milk gavage-induced improvements in long-term spatial learning. In the peripheral immune system, UK4 increased the prevalence of Treg cells and interleukin 10 levels, whereas Fr1 ameliorated the milk gavage stress-induced elevation in neutrophil levels and CXCL1 levels. Analysis of the gut microbiota revealed that both kefirs significantly changed the composition and functional capacity of the host microbiota, where specific bacterial species were changed in a kefir-dependent manner. Furthermore, both kefirs increased the capacity of the gut microbiota to produce GABA, which was linked to an increased prevalence in Lactobacillus reuteri. Conclusions: Altogether, these data show that kefir can signal through the microbiota-gut-immune-brain axis and modulate host behaviour. In addition, different kefirs may direct the microbiota toward distinct immunological and behavioural modulatory effects. These results indicate that kefir can positively modulate specific aspects of the microbiota-gut-brain axis and support the broadening of the definition of psychobiotic to include kefir fermented foods. [MediaObject not available: see fulltext.]

@article{
 title = {Encapsulated cyclosporine does not change the composition of the human microbiota when assessed ex vivo and in vivo},
 type = {article},
 year = {2020},
 keywords = {16S rRNA gene sequencing,Composition,Cyclosporine A,Functionality,Human microbiota,Short-chain fatty acids},
 pages = {854},
 volume = {69},
 websites = {/pmc/articles/PMC7451034/,/pmc/articles/PMC7451034/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451034/},
 publisher = {Microbiology Society},
 id = {09b95955-c9ee-34e3-9daa-190538a17f10},
 created = {2025-07-07T13:25:26.314Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:12.212Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction: Management of steroid-refractory ulcerative colitis has predominantly involved treatment with systemic cyclosporine A (CyA) and infliximab. Aim. The purpose of this study was to assess the effect of using a colon-targeted delivery system CyA formulation on the composition and functionality of the gut microbiota. Methodology: Ex vivo faecal fermentations from six healthy control subjects were treated with coated minispheres (SmPill) with (+) or without (−) CyA and compared with a non-treated control in a model colon system. In addition, the in vivo effect of the SmPill+CyA formulation was investigated by analysing the gut microbiota in faecal samples collected before the administration of SmPill+CyA and after 7 consecutive days of administration from eight healthy subjects who participated in a pilot study. Results: Analysis of faecal samples by 16S rRNA gene sequencing indicated little variation in the diversity or relative abundance of the microbiota composition before or after treatment with SmPill minispheres with or without CyA ex vivo or with CyA in vivo. Short-chain fatty acid profiles were evaluated using gas chromatography, showing an increase in the concentration of n-butyrate (P=0.02) and acetate (P=0.32) in the faecal fermented samples incubated in the presence of SmPill minispheres with or without CyA. This indicated that increased acetate and butyrate production was attributed to a component of the coated minispheres rather than an effect of CyA on the microbiota. Butyrate and acetate levels also increased significantly (P=0.05 for both) in the faecal samples of healthy individuals following 7 days' treatment with SmPill+CyA in the pilot study. Conclusion: SmPill minispheres with or without CyA at the clinically relevant doses tested here have negligible direct effects on the gut microbiota composition. Butyrate and acetate production increased, however, in the presence of the beads in an ex vivo model system as well as in vivo in healthy subjects. Importantly, this study also demonstrates the relevance and value of using ex vivo colon models to predict the in vivo impact of colon-targeted drugs directly on the gut microbiota.},
 bibtype = {article},
 author = {O'Reilly, Catherine and O'Sullivan, Órla and Cotter, Paul D. and O'Connor, Paula M. and Shanahan, Fergus and Cullen, Alan and Rea, Mary C. and Hill, Colin and Coulter, Ivan and Paul Ross, R.},
 doi = {10.1099/JMM.0.001130},
 journal = {Journal of Medical Microbiology},
 number = {6}
}

Introduction: Management of steroid-refractory ulcerative colitis has predominantly involved treatment with systemic cyclosporine A (CyA) and infliximab. Aim. The purpose of this study was to assess the effect of using a colon-targeted delivery system CyA formulation on the composition and functionality of the gut microbiota. Methodology: Ex vivo faecal fermentations from six healthy control subjects were treated with coated minispheres (SmPill) with (+) or without (−) CyA and compared with a non-treated control in a model colon system. In addition, the in vivo effect of the SmPill+CyA formulation was investigated by analysing the gut microbiota in faecal samples collected before the administration of SmPill+CyA and after 7 consecutive days of administration from eight healthy subjects who participated in a pilot study. Results: Analysis of faecal samples by 16S rRNA gene sequencing indicated little variation in the diversity or relative abundance of the microbiota composition before or after treatment with SmPill minispheres with or without CyA ex vivo or with CyA in vivo. Short-chain fatty acid profiles were evaluated using gas chromatography, showing an increase in the concentration of n-butyrate (P=0.02) and acetate (P=0.32) in the faecal fermented samples incubated in the presence of SmPill minispheres with or without CyA. This indicated that increased acetate and butyrate production was attributed to a component of the coated minispheres rather than an effect of CyA on the microbiota. Butyrate and acetate levels also increased significantly (P=0.05 for both) in the faecal samples of healthy individuals following 7 days' treatment with SmPill+CyA in the pilot study. Conclusion: SmPill minispheres with or without CyA at the clinically relevant doses tested here have negligible direct effects on the gut microbiota composition. Butyrate and acetate production increased, however, in the presence of the beads in an ex vivo model system as well as in vivo in healthy subjects. Importantly, this study also demonstrates the relevance and value of using ex vivo colon models to predict the in vivo impact of colon-targeted drugs directly on the gut microbiota.

@article{
 title = {Gut microbiome of a porcine model of metabolic syndrome and HF-pEF},
 type = {article},
 year = {2020},
 keywords = {Animal,Animals,Aoife N O'Donovan,Blood Glucose / metabolism,Cholesterol / blood,Diet,Disease Models,Echocardiography,Female,Florence M Herisson,Gastrointestinal Microbiome / physiology*,High-Fat,Hypertension / metabolism,Hypertension / microbiology*,Inflammation / metabolism,Inflammation / microbiology,Insulin / blood,Insulin Resistance / physiology*,MEDLINE,Metabolic Syndrome / metabolism,Metabolic Syndrome / microbiology*,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Noel M Caplice,Non-U.S. Gov't,Non-alcoholic Fatty Liver Disease / metabolism,Non-alcoholic Fatty Liver Disease / microbiology*,PubMed Abstract,Research Support,Swine,Triglycerides / blood,doi:10.1152/ajpheart.00512.2019,pmid:32031871},
 pages = {H590-H603},
 volume = {318},
 websites = {https://pubmed.ncbi.nlm.nih.gov/32031871/},
 month = {3},
 publisher = {Am J Physiol Heart Circ Physiol},
 day = {1},
 id = {4f7a4843-bff2-3acf-b2f7-a5c6bc6500ea},
 created = {2025-07-07T13:25:26.651Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:12.589Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease. NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.},
 bibtype = {article},
 author = {O'Donovan, Aoife N. and Herisson, Florence M. and Fouhy, Fiona and Ryan, Paul M. and Whelan, Derek and Johnson, Crystal N. and Cluzel, Gaston and Ross, R. Paul and Stanton, Catherine and Caplice, Noel M.},
 doi = {10.1152/AJPHEART.00512.2019},
 journal = {American journal of physiology. Heart and circulatory physiology},
 number = {3}
}

Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease. NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.

@article{
 title = {Metabolomic networks and pathways associated with feed efficiency and related-traits in Duroc and Landrace pigs},
 type = {article},
 year = {2020},
 volume = {10},
 websites = {www.nature.com/scientificreports},
 id = {ec4dd6bb-30c3-35ca-80b5-f1df74a7ae2b},
 created = {2025-07-07T13:25:27.025Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:12.982Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Improving feed efficiency (FE) is a major goal of pig breeding, reducing production costs and providing sustainability to the pig industry. Reliable predictors for fe could assist pig producers. We carried out untargeted blood metabolite profiling in uncastrated males from Danbred Duroc (n = 59) and Danbred Landrace (n = 50) pigs at the beginning and end of a FE testing phase to identify biomarkers and biological processes underlying fe and related traits. By applying linear modeling and clustering analyses coupled with WGCNA framework, we identified 102 and 73 relevant metabolites in Duroc and Landrace based on two sampling time points. Among them, choline and pyridoxamine were hub metabolites in Duroc in early testing phase, while, acetoacetate, cholesterol sulfate, xanthine, and deoxyuridine were identified in the end of testing. In Landrace, cholesterol sulfate, thiamine, L-methionine, chenodeoxycholate were identified at early testing phase, while, D-glutamate, pyridoxamine, deoxycytidine, and L-2-aminoadipate were found at the end of testing. Validation of these results in larger populations could establish fe prediction using metabolomics biomarkers. We conclude that it is possible to identify a link between blood metabolite profiles and FE. These results could lead to improved nutrient utilization, reduced production costs, and increased fe. With the expanding human population and requirement for nutrient-rich food, there is an increasing demand for improvement of meat production, but simultaneously, to decrease the input costs in terms of feed 1. Thus, feed efficiency (FE) is the most important trait in commercial pig farming 2 as increasing the amount of meat produced per feed is beneficial both economically and environmentally. Thereby, improving FE is beneficial for producers and increases the sustainability of pork meat production. Fortunately, FE is a highly heritable trait in Danish pigs (ranging from 0.34 in Duroc to 0.40 in Landrace), thus suitable for the genetic selection of pigs with high breeding values in breeding programs aimed at improving this economically important phenotype 3. Since FE cannot be measured directly, feed conversion ratio (FCR) and residual feed intake (RFI) have been used to evaluate the animal efficiency 4. FCR determines the ratio of feed intake (FI) to output and found to correlate with growth rate and body weight 3,5. RFI calculates the difference between the actual and expected FI 6 predicted based on production traits such as average daily gain (ADG) 7. ADG is also considered important in commercial pig production as pigs with higher ADG can achieve a target market weight within a shorter period than those with lower ADG, thereby saving feeding costs 8. Thus, selection for RFI has proved to be effective in improving the FE in pigs 3,9,10. Selection for FCR will results in co-selection for other traits, such as body composition and ADG. In contrast, RFI selects for increased metabolic efficiency without the same side effects 11-13. RFI and FCR are well correlated, with a reported correlation of over 0.7 in the literature 3. As part of the existing genetic determinants of FE, genome-wide association studies (GWAS) and differential expression (DE) analyses have reported a large number of polymorphism and genes for RFI or FCR in pigs 9,14. However, despite these efforts, FE is a complex trait with many aspects involved and the functional molecular background is still somewhat elusive 1. Among the approaches, the metabolomics profile reveals the relationship between animal genetics and physiological phenotypes 15 , thereby increasing the fundamental understanding of},
 bibtype = {article},
 author = {Adriano Okstoft Carmelo, Victor and Banerjee, Priyanka and Jarles Da Silva Diniz, Wellison and Kadarmideen, Haja N},
 doi = {10.1038/s41598-019-57182-4},
 journal = {Scientific Report},
 number = {255}
}

Improving feed efficiency (FE) is a major goal of pig breeding, reducing production costs and providing sustainability to the pig industry. Reliable predictors for fe could assist pig producers. We carried out untargeted blood metabolite profiling in uncastrated males from Danbred Duroc (n = 59) and Danbred Landrace (n = 50) pigs at the beginning and end of a FE testing phase to identify biomarkers and biological processes underlying fe and related traits. By applying linear modeling and clustering analyses coupled with WGCNA framework, we identified 102 and 73 relevant metabolites in Duroc and Landrace based on two sampling time points. Among them, choline and pyridoxamine were hub metabolites in Duroc in early testing phase, while, acetoacetate, cholesterol sulfate, xanthine, and deoxyuridine were identified in the end of testing. In Landrace, cholesterol sulfate, thiamine, L-methionine, chenodeoxycholate were identified at early testing phase, while, D-glutamate, pyridoxamine, deoxycytidine, and L-2-aminoadipate were found at the end of testing. Validation of these results in larger populations could establish fe prediction using metabolomics biomarkers. We conclude that it is possible to identify a link between blood metabolite profiles and FE. These results could lead to improved nutrient utilization, reduced production costs, and increased fe. With the expanding human population and requirement for nutrient-rich food, there is an increasing demand for improvement of meat production, but simultaneously, to decrease the input costs in terms of feed 1. Thus, feed efficiency (FE) is the most important trait in commercial pig farming 2 as increasing the amount of meat produced per feed is beneficial both economically and environmentally. Thereby, improving FE is beneficial for producers and increases the sustainability of pork meat production. Fortunately, FE is a highly heritable trait in Danish pigs (ranging from 0.34 in Duroc to 0.40 in Landrace), thus suitable for the genetic selection of pigs with high breeding values in breeding programs aimed at improving this economically important phenotype 3. Since FE cannot be measured directly, feed conversion ratio (FCR) and residual feed intake (RFI) have been used to evaluate the animal efficiency 4. FCR determines the ratio of feed intake (FI) to output and found to correlate with growth rate and body weight 3,5. RFI calculates the difference between the actual and expected FI 6 predicted based on production traits such as average daily gain (ADG) 7. ADG is also considered important in commercial pig production as pigs with higher ADG can achieve a target market weight within a shorter period than those with lower ADG, thereby saving feeding costs 8. Thus, selection for RFI has proved to be effective in improving the FE in pigs 3,9,10. Selection for FCR will results in co-selection for other traits, such as body composition and ADG. In contrast, RFI selects for increased metabolic efficiency without the same side effects 11-13. RFI and FCR are well correlated, with a reported correlation of over 0.7 in the literature 3. As part of the existing genetic determinants of FE, genome-wide association studies (GWAS) and differential expression (DE) analyses have reported a large number of polymorphism and genes for RFI or FCR in pigs 9,14. However, despite these efforts, FE is a complex trait with many aspects involved and the functional molecular background is still somewhat elusive 1. Among the approaches, the metabolomics profile reveals the relationship between animal genetics and physiological phenotypes 15 , thereby increasing the fundamental understanding of

@article{
 title = {Oxidant-induced modifications in the mucosal transcriptome and circulating metabolome of Atlantic salmon},
 type = {article},
 year = {2020},
 keywords = {Amoebic gill disease,Aquaculture,Disinfectant,Metabolomics,Mucosal immunity,Oxidative stress,Peroxide},
 pages = {105625},
 volume = {227},
 month = {10},
 publisher = {Elsevier},
 day = {1},
 id = {17a4b4fc-df08-34e7-82d9-8cd39e826309},
 created = {2025-07-07T13:25:27.351Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:13.241Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Here we report the molecular networks associated with the mucosal and systemic responses to peracetic acid (PAA), a candidate oxidative chemotherapeutic in Atlantic salmon (Salmo salar). Smolts were exposed to different therapeutic doses (0, 0.6 and 2.4 mg/L) of PAA for 5 min, followed by a re-exposure to the same concentrations for 30 min 2 weeks later. PAA-exposed groups have higher external welfare score alterations, especially 2 weeks after the re-exposure. Cases of fin damage and scale loss were prevalent in the PAA-exposed groups. Transcriptomic profiling of mucosal tissues revealed that the skin had 12.5 % more differentially regulated genes (DEGs) than the gills following PAA exposure. The largest cluster of DEGs, both in the skin and gills, were involved in tissue extracellular matrix and metabolism. There were 22 DEGs common to both mucosal tissues, which were represented primarily by genes involved in the biophysical integrity of the mucosal barrier, including cadherin, collagen I α 2 chain, mucin-2 and spondin 1a. The absence of significant clustering in the plasma metabolomes amongst the three treatment groups indicates that PAA treatment did not induce any global metabolomic disturbances. Nonetheless, five metabolites with known functions during oxidative stress were remarkably affected by PAA treatments such as citrulline, histidine, tryptophan, methionine and trans-4-hydroxyproline. Collectively, these results indicate that salmon were able to mount mucosal and systemic adaptive responses to therapeutic doses of PAA and that the molecules identified are potential markers for assessing the health and welfare consequences of oxidant exposure.},
 bibtype = {article},
 author = {Lazado, Carlo C. and Pedersen, Lars Flemming and Kirste, Katrine H. and Soleng, Malene and Breiland, Mette W. and Timmerhaus, Gerrit},
 doi = {10.1016/J.AQUATOX.2020.105625},
 journal = {Aquatic Toxicology}
}

Here we report the molecular networks associated with the mucosal and systemic responses to peracetic acid (PAA), a candidate oxidative chemotherapeutic in Atlantic salmon (Salmo salar). Smolts were exposed to different therapeutic doses (0, 0.6 and 2.4 mg/L) of PAA for 5 min, followed by a re-exposure to the same concentrations for 30 min 2 weeks later. PAA-exposed groups have higher external welfare score alterations, especially 2 weeks after the re-exposure. Cases of fin damage and scale loss were prevalent in the PAA-exposed groups. Transcriptomic profiling of mucosal tissues revealed that the skin had 12.5 % more differentially regulated genes (DEGs) than the gills following PAA exposure. The largest cluster of DEGs, both in the skin and gills, were involved in tissue extracellular matrix and metabolism. There were 22 DEGs common to both mucosal tissues, which were represented primarily by genes involved in the biophysical integrity of the mucosal barrier, including cadherin, collagen I α 2 chain, mucin-2 and spondin 1a. The absence of significant clustering in the plasma metabolomes amongst the three treatment groups indicates that PAA treatment did not induce any global metabolomic disturbances. Nonetheless, five metabolites with known functions during oxidative stress were remarkably affected by PAA treatments such as citrulline, histidine, tryptophan, methionine and trans-4-hydroxyproline. Collectively, these results indicate that salmon were able to mount mucosal and systemic adaptive responses to therapeutic doses of PAA and that the molecules identified are potential markers for assessing the health and welfare consequences of oxidant exposure.

@article{
 title = {Prebiotic administration modulates gut microbiota and faecal short-chain fatty acid concentrations but does not prevent chronic intermittent hypoxia-induced apnoea and hypertension in adult rats: Role of the microbiota-gut-brain axis in CIH-induced cardiorespiratory dysfunction},
 type = {article},
 year = {2020},
 keywords = {SCFA},
 volume = {59},
 websites = {http://www.thelancet.com/article/S2352396420303443/fulltext,http://www.thelancet.com/article/S2352396420303443/abstract,https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(20)30344-3/abstract},
 month = {9},
 publisher = {Elsevier B.V.},
 day = {1},
 id = {47b78574-85d5-3006-8a7a-ed92b75729d4},
 created = {2025-07-07T13:25:27.709Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:13.607Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Evidence is accruing to suggest that microbiota-gut-brain signalling plays a regulatory role in cardiorespiratory physiology. Chronic intermittent hypoxia (CIH), modelling human sleep apnoea, affects gut microbiota composition and elicits cardiorespiratory morbidity. We investigated if treatment with prebiotics ameliorates cardiorespiratory dysfunction in CIH-exposed rats. Methods: Adult male rats were exposed to CIH (96 cycles/day, 6.0% O2 at nadir) for 14 consecutive days with and without prebiotic supplementation (fructo- and galacto-oligosaccharides) beginning two weeks prior to gas exposures. Findings: CIH increased apnoea index and caused hypertension. CIH exposure had modest effects on the gut microbiota, decreasing the relative abundance of Lactobacilli species, but had no effect on microbial functional characteristics. Faecal short-chain fatty acid (SCFA) concentrations, plasma and brainstem pro-inflammatory cytokine concentrations and brainstem neurochemistry were unaffected by exposure to CIH. Prebiotic administration modulated gut microbiota composition and diversity, altering gut-metabolic (GMMs) and gut-brain (GBMs) modules and increased faecal acetic and propionic acid concentrations, but did not prevent adverse CIH-induced cardiorespiratory phenotypes. Interpretation: CIH-induced cardiorespiratory dysfunction is not dependant upon changes in microbial functional characteristics and decreased faecal SCFA concentrations. Prebiotic-related modulation of microbial function and resultant increases in faecal SCFAs were not sufficient to prevent CIH-induced apnoea and hypertension in our model. Our results do not exclude the potential for microbiota-gut-brain axis involvement in OSA-related cardiorespiratory morbidity, but they demonstrate that in a relatively mild model of CIH, sufficient to evoke classic cardiorespiratory dysfunction, such changes are not obligatory for the development of morbidity, but may become relevant in the elaboration and maintenance of cardiorespiratory morbidity with progressive disease. Funding: Department of Physiology and APC Microbiome Ireland, University College Cork, Ireland. APC Microbiome Ireland is funded by Science Foundation Ireland, through the Government's National Development Plan.},
 bibtype = {article},
 author = {O'Connor, Karen M. and Lucking, Eric F. and Bastiaanssen, Thomaz F.S. and Peterson, Veronica L. and Crispie, Fiona and Cotter, Paul D. and Clarke, Gerard and Cryan, John F. and O'Halloran, Ken D.},
 doi = {10.1016/J.EBIOM.2020.102968/ATTACHMENT/9B13E164-2DF4-4796-BAE3-E3FF37C82ECF/MMC2.DOCX},
 journal = {EBioMedicine}
}

Background: Evidence is accruing to suggest that microbiota-gut-brain signalling plays a regulatory role in cardiorespiratory physiology. Chronic intermittent hypoxia (CIH), modelling human sleep apnoea, affects gut microbiota composition and elicits cardiorespiratory morbidity. We investigated if treatment with prebiotics ameliorates cardiorespiratory dysfunction in CIH-exposed rats. Methods: Adult male rats were exposed to CIH (96 cycles/day, 6.0% O2 at nadir) for 14 consecutive days with and without prebiotic supplementation (fructo- and galacto-oligosaccharides) beginning two weeks prior to gas exposures. Findings: CIH increased apnoea index and caused hypertension. CIH exposure had modest effects on the gut microbiota, decreasing the relative abundance of Lactobacilli species, but had no effect on microbial functional characteristics. Faecal short-chain fatty acid (SCFA) concentrations, plasma and brainstem pro-inflammatory cytokine concentrations and brainstem neurochemistry were unaffected by exposure to CIH. Prebiotic administration modulated gut microbiota composition and diversity, altering gut-metabolic (GMMs) and gut-brain (GBMs) modules and increased faecal acetic and propionic acid concentrations, but did not prevent adverse CIH-induced cardiorespiratory phenotypes. Interpretation: CIH-induced cardiorespiratory dysfunction is not dependant upon changes in microbial functional characteristics and decreased faecal SCFA concentrations. Prebiotic-related modulation of microbial function and resultant increases in faecal SCFAs were not sufficient to prevent CIH-induced apnoea and hypertension in our model. Our results do not exclude the potential for microbiota-gut-brain axis involvement in OSA-related cardiorespiratory morbidity, but they demonstrate that in a relatively mild model of CIH, sufficient to evoke classic cardiorespiratory dysfunction, such changes are not obligatory for the development of morbidity, but may become relevant in the elaboration and maintenance of cardiorespiratory morbidity with progressive disease. Funding: Department of Physiology and APC Microbiome Ireland, University College Cork, Ireland. APC Microbiome Ireland is funded by Science Foundation Ireland, through the Government's National Development Plan.

@article{
 title = {Staphylococcus aureus induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes},
 type = {article},
 year = {2020},
 keywords = {UL16-binding protein 2 (ULBP2),antibiotic resistance,bacterial virulence,cell metabolism,immune evasion,immunology,methicillin-resistant Staphylococcus aureus (MRSA),monocyte,natural killer group 2D (NKG2D)},
 pages = {11803-11821},
 volume = {295},
 websites = {http://www.jbc.org/article/S0021925817484778/fulltext,http://www.jbc.org/article/S0021925817484778/abstract,https://www.jbc.org/article/S0021-9258(17)48477-8/abstract},
 month = {8},
 publisher = {American Society for Biochemistry and Molecular Biology Inc.},
 day = {14},
 id = {0ef71c27-4b42-3878-b28b-f73031c7fa9c},
 created = {2025-07-07T13:25:28.066Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:13.965Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Staphylococcus aureus is among the leading causes of bacterial infections worldwide. The pathogenicity and establishment of S. aureus infections are tightly linked to its ability to modulate host immunity. Persistent infections are often associated with mutant staphylococcal strains that have decreased susceptibility to antibiotics; however, little is known about how these mutations influence bacterial interaction with the host immune system. Here, we discovered that clinical S. aureus isolates activate human monocytes, leading to cell-surface expression of immune stimulatory natural killer group 2D (NKG2D) ligands on the monocytes. We found that expression of the NKG2D ligand ULBP2 (UL16-binding protein 2) is associated with bacterial degradability and phagolysosomal activity. Moreover, S. aureus–induced ULBP2 expression was linked to altered host cell metabolism, including increased cytoplasmic (iso)citrate levels, reduced glycolytic flux, and functional mitochondrial activity. Interestingly, we found that the ability of S. aureus to induce ULBP2 and proinflammatory cytokines in human monocytes depends on a functional ClpP protease in S. aureus. These findings indicate that S. aureus activates ULBP2 in human monocytes through immunometabolic mechanisms and reveal that clpP inactivation may function as a potential immune evasion mechanism. Our results provide critical insight into the interplay between the host immune system and S. aureus that has evolved under the dual selective pressure of host immune responses and antibiotic treatment. Our discovery of an immune stimulatory pathway consisting of human monocyte-based defense against S. aureus suggests that targeting the NKG2D pathway holds potential for managing persistent staphylococcal infections.},
 bibtype = {article},
 author = {Mellergaard, Maiken and Høgh, Rikke Illum and Lund, Astrid and Aldana, Blanca Irene and Guérillot, Romain and Møller, Sofie Hedlund and Hayes, Ashleigh S. and Panagiotopoulou, Nafsika and Frimand, Zofija and Jepsen, Stine Dam and Hansen, Camilla Hartmann Friis and Andresen, Lars and Larsen, Anders Rhod and Peleg, Anton Y. and Stinear, Timothy P. and Howden, Benjamin P. and Waagepetersen, Helle S. and Frees, Dorte and Skov, Søren},
 doi = {10.1074/JBC.RA120.012673/ATTACHMENT/E1960645-E916-45A2-8BDE-4B87A6E08B91/MMC1.PDF},
 journal = {Journal of Biological Chemistry},
 number = {33}
}

Staphylococcus aureus is among the leading causes of bacterial infections worldwide. The pathogenicity and establishment of S. aureus infections are tightly linked to its ability to modulate host immunity. Persistent infections are often associated with mutant staphylococcal strains that have decreased susceptibility to antibiotics; however, little is known about how these mutations influence bacterial interaction with the host immune system. Here, we discovered that clinical S. aureus isolates activate human monocytes, leading to cell-surface expression of immune stimulatory natural killer group 2D (NKG2D) ligands on the monocytes. We found that expression of the NKG2D ligand ULBP2 (UL16-binding protein 2) is associated with bacterial degradability and phagolysosomal activity. Moreover, S. aureus–induced ULBP2 expression was linked to altered host cell metabolism, including increased cytoplasmic (iso)citrate levels, reduced glycolytic flux, and functional mitochondrial activity. Interestingly, we found that the ability of S. aureus to induce ULBP2 and proinflammatory cytokines in human monocytes depends on a functional ClpP protease in S. aureus. These findings indicate that S. aureus activates ULBP2 in human monocytes through immunometabolic mechanisms and reveal that clpP inactivation may function as a potential immune evasion mechanism. Our results provide critical insight into the interplay between the host immune system and S. aureus that has evolved under the dual selective pressure of host immune responses and antibiotic treatment. Our discovery of an immune stimulatory pathway consisting of human monocyte-based defense against S. aureus suggests that targeting the NKG2D pathway holds potential for managing persistent staphylococcal infections.

@article{
 title = {Chronic exposure of soybean plants to nanomolar cadmium reveals specific additional high-affinity targets of cadmium toxicity},
 type = {article},
 year = {2020},
 keywords = {Cadmium* / toxicity,Chlorophyll,Elisa Andresen,Glycine max*,Hendrik Küpper,Lyudmila Lyubenova,MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,PMC7242006,Photosynthesis,Plant Leaves,PubMed Abstract,Research Support,doi:10.1093/jxb/erz530,pmid:31760430},
 pages = {1628-1644},
 volume = {71},
 websites = {https://pubmed.ncbi.nlm.nih.gov/31760430/},
 month = {2},
 publisher = {J Exp Bot},
 day = {19},
 id = {41d05d21-6e7d-33fb-b557-0e199860f6a9},
 created = {2025-07-07T13:25:28.456Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:14.298Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Solving the global environmental and agricultural problem of chronic low-level cadmium (Cd) exposure requires better mechanistic understanding. Here, soybean (Glycine max) plants were exposed to Cd concentrations ranging from 0.5 nM (background concentration, control) to 3 μM. Plants were cultivated hydroponically under non-nodulating conditions for 10 weeks. Toxicity symptoms, net photosynthetic oxygen production and photosynthesis biophysics (chlorophyll fluorescence: Kautsky and OJIP) were measured in young mature leaves. Cd binding to proteins [metalloproteomics by HPLC-inductively coupled plasma (ICP)-MS] and Cd ligands in light-harvesting complex II (LHCII) [X-ray absorption near edge structure (XANES)], and accumulation of elements, chloropyll, and metabolites were determined in leaves after harvest. A distinct threshold concentration of toxicity onset (140 nM) was apparent in strongly decreased growth, the switch-like pattern for nutrient uptake and metal accumulation, and photosynthetic fluorescence parameters such as φRE10 (OJIP) and saturation of the net photosynthetic oxygen release rate. XANES analyses of isolated LHCII revealed that Cd was bound to nitrogen or oxygen (and not sulfur) atoms. Nutrient deficiencies caused by inhibited uptake could be due to transporter blockage by Cd ions. The changes in specific fluorescence kinetic parameters indicate electrons not being transferred from PSII to PSI. Inhibition of photosynthesis combined with inhibition of root function could explain why amino acid and carbohydrate metabolism decreased in favour of molecules involved in Cd stress tolerance (e.g. antioxidative system and detoxifying ligands).},
 bibtype = {article},
 author = {Andresen, Elisa and Lyubenova, Lyudmila and Hubáček, Tomáš and Bokhari, Syed Nadeem Hussain and Matoušková, Šárka and Mijovilovich, Ana and Rohovec, Jan and Küpper, Hendrik},
 doi = {10.1093/JXB/ERZ530},
 journal = {Journal of experimental botany},
 number = {4}
}

Solving the global environmental and agricultural problem of chronic low-level cadmium (Cd) exposure requires better mechanistic understanding. Here, soybean (Glycine max) plants were exposed to Cd concentrations ranging from 0.5 nM (background concentration, control) to 3 μM. Plants were cultivated hydroponically under non-nodulating conditions for 10 weeks. Toxicity symptoms, net photosynthetic oxygen production and photosynthesis biophysics (chlorophyll fluorescence: Kautsky and OJIP) were measured in young mature leaves. Cd binding to proteins [metalloproteomics by HPLC-inductively coupled plasma (ICP)-MS] and Cd ligands in light-harvesting complex II (LHCII) [X-ray absorption near edge structure (XANES)], and accumulation of elements, chloropyll, and metabolites were determined in leaves after harvest. A distinct threshold concentration of toxicity onset (140 nM) was apparent in strongly decreased growth, the switch-like pattern for nutrient uptake and metal accumulation, and photosynthetic fluorescence parameters such as φRE10 (OJIP) and saturation of the net photosynthetic oxygen release rate. XANES analyses of isolated LHCII revealed that Cd was bound to nitrogen or oxygen (and not sulfur) atoms. Nutrient deficiencies caused by inhibited uptake could be due to transporter blockage by Cd ions. The changes in specific fluorescence kinetic parameters indicate electrons not being transferred from PSII to PSI. Inhibition of photosynthesis combined with inhibition of root function could explain why amino acid and carbohydrate metabolism decreased in favour of molecules involved in Cd stress tolerance (e.g. antioxidative system and detoxifying ligands).

@article{
 title = {Prokaryotic viperins produce diverse antiviral molecules},
 type = {article},
 year = {2020},
 keywords = {polar},
 pages = {120-124},
 volume = {589},
 websites = {https://www.nature.com/articles/s41586-020-2762-2},
 month = {9},
 publisher = {Nature Publishing Group},
 day = {16},
 id = {7e61b953-7d4e-3981-bda5-53d64e8c5613},
 created = {2025-07-07T13:25:28.782Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:28.782Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Viperin is an interferon-induced cellular protein that is conserved in animals1. It has previously been shown to inhibit the replication of multiple viruses by producing the ribonucleotide 3′-deoxy-3′,4′-didehydro (ddh)-cytidine triphosphate (ddhCTP), which acts as a chain terminator for viral RNA polymerase2. Here we show that eukaryotic viperin originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins produce a set of modified ribonucleotides that include ddhCTP, ddh-guanosine triphosphate (ddhGTP) and ddh-uridine triphosphate (ddhUTP). We further show that prokaryotic viperins protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting that it has an antiviral mechanism of action similar to that of animal viperin. Our results reveal a class of potential natural antiviral compounds produced by bacterial immune systems. Eukaryotic viperins originated from a clade of bacterial and archaeal proteins that catalyse the production of antiviral molecules.},
 bibtype = {article},
 author = {Bernheim, Aude and Millman, Adi and Ofir, Gal and Meitav, Gilad and Avraham, Carmel and Shomar, Helena and Rosenberg, Masha M. and Tal, Nir and Melamed, Sarah and Amitai, Gil and Sorek, Rotem},
 doi = {10.1038/s41586-020-2762-2},
 journal = {Nature 2020 589:7840},
 number = {7840}
}

Viperin is an interferon-induced cellular protein that is conserved in animals1. It has previously been shown to inhibit the replication of multiple viruses by producing the ribonucleotide 3′-deoxy-3′,4′-didehydro (ddh)-cytidine triphosphate (ddhCTP), which acts as a chain terminator for viral RNA polymerase2. Here we show that eukaryotic viperin originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins produce a set of modified ribonucleotides that include ddhCTP, ddh-guanosine triphosphate (ddhGTP) and ddh-uridine triphosphate (ddhUTP). We further show that prokaryotic viperins protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting that it has an antiviral mechanism of action similar to that of animal viperin. Our results reveal a class of potential natural antiviral compounds produced by bacterial immune systems. Eukaryotic viperins originated from a clade of bacterial and archaeal proteins that catalyse the production of antiviral molecules.

@article{
 title = {Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse},
 type = {article},
 year = {2020},
 keywords = {Behaviour,Brain,GABA,Immunity,Kefir,Lactobacillus,Microbiota,Mouse,Reward,Serotonin},
 volume = {8},
 month = {5},
 publisher = {BioMed Central Ltd.},
 day = {18},
 id = {c5918614-0090-3110-9dff-ba57035e8870},
 created = {2025-07-07T13:25:29.125Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:14.715Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Mounting evidence suggests a role for the gut microbiota in modulating brain physiology and behaviour, through bi-directional communication, along the gut-brain axis. As such, the gut microbiota represents a potential therapeutic target for influencing centrally mediated events and host behaviour. It is thus notable that the fermented milk beverage kefir has recently been shown to modulate the composition of the gut microbiota in mice. It is unclear whether kefirs have differential effects on microbiota-gut-brain axis and whether they can modulate host behaviour per se. Methods: To address this, two distinct kefirs (Fr1 and UK4), or unfermented milk control, were administered to mice that underwent a battery of tests to characterise their behavioural phenotype. In addition, shotgun metagenomic sequencing of ileal, caecal and faecal matter was performed, as was faecal metabolome analysis. Finally, systemic immunity measures and gut serotonin levels were assessed. Statistical analyses were performed by ANOVA followed by Dunnett's post hoc test or Kruskal-Wallis test followed by Mann-Whitney U test. Results: Fr1 ameliorated the stress-induced decrease in serotonergic signalling in the colon and reward-seeking behaviour in the saccharin preference test. On the other hand, UK4 decreased repetitive behaviour and ameliorated stress-induced deficits in reward-seeking behaviour. Furthermore, UK4 increased fear-dependent contextual memory, yet decreased milk gavage-induced improvements in long-term spatial learning. In the peripheral immune system, UK4 increased the prevalence of Treg cells and interleukin 10 levels, whereas Fr1 ameliorated the milk gavage stress-induced elevation in neutrophil levels and CXCL1 levels. Analysis of the gut microbiota revealed that both kefirs significantly changed the composition and functional capacity of the host microbiota, where specific bacterial species were changed in a kefir-dependent manner. Furthermore, both kefirs increased the capacity of the gut microbiota to produce GABA, which was linked to an increased prevalence in Lactobacillus reuteri. Conclusions: Altogether, these data show that kefir can signal through the microbiota-gut-immune-brain axis and modulate host behaviour. In addition, different kefirs may direct the microbiota toward distinct immunological and behavioural modulatory effects. These results indicate that kefir can positively modulate specific aspects of the microbiota-gut-brain axis and support the broadening of the definition of psychobiotic to include kefir fermented foods. [MediaObject not available: see fulltext.]},
 bibtype = {article},
 author = {Van De Wouw, Marcel and Walsh, Aaron M. and Crispie, Fiona and Van Leuven, Lucas and Lyte, Joshua M. and Boehme, Marcus and Clarke, Gerard and Dinan, Timothy G. and Cotter, Paul D. and Cryan, John F.},
 doi = {10.1186/s40168-020-00846-5},
 journal = {Microbiome},
 number = {1}
}

Background: Mounting evidence suggests a role for the gut microbiota in modulating brain physiology and behaviour, through bi-directional communication, along the gut-brain axis. As such, the gut microbiota represents a potential therapeutic target for influencing centrally mediated events and host behaviour. It is thus notable that the fermented milk beverage kefir has recently been shown to modulate the composition of the gut microbiota in mice. It is unclear whether kefirs have differential effects on microbiota-gut-brain axis and whether they can modulate host behaviour per se. Methods: To address this, two distinct kefirs (Fr1 and UK4), or unfermented milk control, were administered to mice that underwent a battery of tests to characterise their behavioural phenotype. In addition, shotgun metagenomic sequencing of ileal, caecal and faecal matter was performed, as was faecal metabolome analysis. Finally, systemic immunity measures and gut serotonin levels were assessed. Statistical analyses were performed by ANOVA followed by Dunnett's post hoc test or Kruskal-Wallis test followed by Mann-Whitney U test. Results: Fr1 ameliorated the stress-induced decrease in serotonergic signalling in the colon and reward-seeking behaviour in the saccharin preference test. On the other hand, UK4 decreased repetitive behaviour and ameliorated stress-induced deficits in reward-seeking behaviour. Furthermore, UK4 increased fear-dependent contextual memory, yet decreased milk gavage-induced improvements in long-term spatial learning. In the peripheral immune system, UK4 increased the prevalence of Treg cells and interleukin 10 levels, whereas Fr1 ameliorated the milk gavage stress-induced elevation in neutrophil levels and CXCL1 levels. Analysis of the gut microbiota revealed that both kefirs significantly changed the composition and functional capacity of the host microbiota, where specific bacterial species were changed in a kefir-dependent manner. Furthermore, both kefirs increased the capacity of the gut microbiota to produce GABA, which was linked to an increased prevalence in Lactobacillus reuteri. Conclusions: Altogether, these data show that kefir can signal through the microbiota-gut-immune-brain axis and modulate host behaviour. In addition, different kefirs may direct the microbiota toward distinct immunological and behavioural modulatory effects. These results indicate that kefir can positively modulate specific aspects of the microbiota-gut-brain axis and support the broadening of the definition of psychobiotic to include kefir fermented foods. [MediaObject not available: see fulltext.]

@article{
 title = {Interventional Influence of the Intestinal Microbiome Through Dietary Intervention and Bowel Cleansing Might Improve Motor Symptoms in Parkinson’s Disease},
 type = {article},
 year = {2020},
 keywords = {butyric acid,enema,microbiome,parkinson,s disease,vegetarian diet},
 pages = {376},
 volume = {9},
 websites = {https://www.mdpi.com/2073-4409/9/2/376},
 month = {2},
 day = {6},
 id = {5925b0f6-9ade-306c-a863-0c5adca86fbd},
 created = {2025-07-07T13:25:29.457Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:15.084Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {<p>The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson’s disease (PD). In the pathogenesis of PD, the role of the gut has been previously established. In conjunction with a better understanding of the intestinal microbiome, a link to the misfolding and spread of alpha-synuclein via inflammatory processes within the gut is discussed. In a case-control study, we assessed the gut microbiome of 54 PD patients and 32 healthy controls (HC). Additionally, we tested in this proof-of-concept study whether dietary intervention alone or additional physical colon cleaning may lead to changes of the gut microbiome in PD. 16 PD patients underwent a well-controlled balanced, ovo-lacto vegetarian diet intervention including short fatty acids for 14 days. 10 of those patients received additional treatment with daily fecal enema over 8 days. Stool samples were collected before and after 14 days of intervention. In comparison to HC, we could confirm previously reported PD associated microbiome changes. The UDPRS III significantly improved and the levodopa-equivalent daily dose decreased after vegetarian diet and fecal enema in a one-year follow-up. Additionally, we observed a significant association between the gut microbiome diversity and the UPDRS III and the abundance of Ruminococcaceae. Additionally, the abundance of Clostridiaceae was significantly reduced after enema. Dietary intervention and bowel cleansing may provide an additional non-pharmacologic therapeutic option for PD patients.</p>},
 bibtype = {article},
 author = {Hegelmaier, Tobias and Lebbing, Marco and Duscha, Alexander and Tomaske, Laura and Tönges, Lars and Holm, Jacob Bak and Bjørn Nielsen, Henrik and Gatermann, Sören G. and Przuntek, Horst and Haghikia, Aiden},
 doi = {10.3390/cells9020376},
 journal = {Cells},
 number = {2}
}

The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson’s disease (PD). In the pathogenesis of PD, the role of the gut has been previously established. In conjunction with a better understanding of the intestinal microbiome, a link to the misfolding and spread of alpha-synuclein via inflammatory processes within the gut is discussed. In a case-control study, we assessed the gut microbiome of 54 PD patients and 32 healthy controls (HC). Additionally, we tested in this proof-of-concept study whether dietary intervention alone or additional physical colon cleaning may lead to changes of the gut microbiome in PD. 16 PD patients underwent a well-controlled balanced, ovo-lacto vegetarian diet intervention including short fatty acids for 14 days. 10 of those patients received additional treatment with daily fecal enema over 8 days. Stool samples were collected before and after 14 days of intervention. In comparison to HC, we could confirm previously reported PD associated microbiome changes. The UDPRS III significantly improved and the levodopa-equivalent daily dose decreased after vegetarian diet and fecal enema in a one-year follow-up. Additionally, we observed a significant association between the gut microbiome diversity and the UPDRS III and the abundance of Ruminococcaceae. Additionally, the abundance of Clostridiaceae was significantly reduced after enema. Dietary intervention and bowel cleansing may provide an additional non-pharmacologic therapeutic option for PD patients.

@article{
 title = {Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism},
 type = {article},
 year = {2020},
 pages = {1-14},
 volume = {180},
 websites = {https://doi.org/10.1016/j.cell.2020.02.035},
 id = {175e2b69-4b44-3ee5-aded-3e54128d6907},
 created = {2025-07-07T13:25:29.776Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:15.413Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Duscha2020},
 private_publication = {false},
 abstract = {Graphical Abstract Highlights d PA is reduced in MS patients, particularly early after disease manifestation d PA reduction is associated with an altered gut microbiome composition d After 14 days of PA supplementation, Treg cell/TH17 imbalance was restored d Longitudinal PA supplementation might have clinical implications Correspondence aiden.haghikia@rub.de In Brief Supplementation of the short-chain fatty acid propionic acid (PA) in multiple sclerosis (MS) patients reverses the Treg cell/Th17 cell imbalance via increased Treg cell induction and enhancement of Treg cell function and is associated with disease course improvement.},
 bibtype = {article},
 author = {Duscha, Alexander and Gisevius, Barbara and Hirschberg, Sarah and Linker, Ralf A and Gold, Ralf and Haghikia, Aiden},
 doi = {10.1016/j.cell.2020.02.035},
 journal = {Cell}
}

Graphical Abstract Highlights d PA is reduced in MS patients, particularly early after disease manifestation d PA reduction is associated with an altered gut microbiome composition d After 14 days of PA supplementation, Treg cell/TH17 imbalance was restored d Longitudinal PA supplementation might have clinical implications Correspondence aiden.haghikia@rub.de In Brief Supplementation of the short-chain fatty acid propionic acid (PA) in multiple sclerosis (MS) patients reverses the Treg cell/Th17 cell imbalance via increased Treg cell induction and enhancement of Treg cell function and is associated with disease course improvement.

@article{
 title = {GlycA, a novel marker for low grade inflammation, reflects gut microbiome diversity and is more accurate than high sensitive CRP in reflecting metabolomic profile},
 type = {article},
 year = {2020},
 keywords = {GlycA,Gut microbiome diversity,Low grade inflammation,Metabolomics,hsCRP},
 volume = {16},
 month = {7},
 publisher = {Springer},
 day = {1},
 id = {940da381-864a-33c7-b69d-cf91f4b9a938},
 created = {2025-10-30T12:05:03.035Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:11.895Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction: Gut microbiota is, along with adipose tissue, recognized as a source for many metabolic and inflammatory disturbances that may contribute to the individual’s state of health. Objectives: We investigated in cross-sectional setting the feasibility of utilizing GlycA, a novel low grade inflammatory marker, and traditional low grade inflammatory marker, high sensitivity CRP (hsCRP), in reflecting serum metabolomics status and gut microbiome diversity. Methods: Fasting serum samples of overweight/obese pregnant women (n = 335, gestational weeks: mean 13.8) were analysed for hsCRP by immunoassay, GlycA and metabolomics status by NMR metabolomics and faecal samples for gut microbiome diversity by metagenomics. The benefits of GlycA as a metabolic marker were investigated against hsCRP. Results: The GlycA concentration correlated with more of the metabolomics markers (144 out of 157), than hsCRP (55 out of 157) (FDR < 0.05). The results remained essentially the same when potential confounding factors known to associate with GlycA and hsCRP levels were taken into account (P < 0.05). This was attributable to the detected correlations between GlycA and the constituents and concentrations of several sized VLDL-particles and branched chain amino acids, which were statistically non-significant with regard to hsCRP. GlycA, but not hsCRP, correlated inversely with gut microbiome diversity. Conclusion: GlycA is a superior marker than hsCRP in assessing the metabolomic profile and gut microbiome diversity. It is proposed that GlycA may act as a novel marker that reflects both the gut microbiome and adipose tissue originated metabolic aberrations; this proposal will need to be verified with regard to clinical outcomes. Clinical trial registration: ClinicalTrials.gov, NCT01922791, August 14, 2013.},
 bibtype = {article},
 author = {Mokkala, Kati and Houttu, Noora and Koivuniemi, Ella and Sørensen, Nikolaj and Nielsen, Henrik Bjørn and Laitinen, Kirsi},
 doi = {10.1007/S11306-020-01695-X},
 journal = {Metabolomics},
 number = {7}
}

Introduction: Gut microbiota is, along with adipose tissue, recognized as a source for many metabolic and inflammatory disturbances that may contribute to the individual’s state of health. Objectives: We investigated in cross-sectional setting the feasibility of utilizing GlycA, a novel low grade inflammatory marker, and traditional low grade inflammatory marker, high sensitivity CRP (hsCRP), in reflecting serum metabolomics status and gut microbiome diversity. Methods: Fasting serum samples of overweight/obese pregnant women (n = 335, gestational weeks: mean 13.8) were analysed for hsCRP by immunoassay, GlycA and metabolomics status by NMR metabolomics and faecal samples for gut microbiome diversity by metagenomics. The benefits of GlycA as a metabolic marker were investigated against hsCRP. Results: The GlycA concentration correlated with more of the metabolomics markers (144 out of 157), than hsCRP (55 out of 157) (FDR < 0.05). The results remained essentially the same when potential confounding factors known to associate with GlycA and hsCRP levels were taken into account (P < 0.05). This was attributable to the detected correlations between GlycA and the constituents and concentrations of several sized VLDL-particles and branched chain amino acids, which were statistically non-significant with regard to hsCRP. GlycA, but not hsCRP, correlated inversely with gut microbiome diversity. Conclusion: GlycA is a superior marker than hsCRP in assessing the metabolomic profile and gut microbiome diversity. It is proposed that GlycA may act as a novel marker that reflects both the gut microbiome and adipose tissue originated metabolic aberrations; this proposal will need to be verified with regard to clinical outcomes. Clinical trial registration: ClinicalTrials.gov, NCT01922791, August 14, 2013.

@article{
 title = {Tumor-Infiltrating T Cells From Clear Cell Renal Cell Carcinoma Patients Recognize Neoepitopes Derived From Point and Frameshift Mutations},
 type = {article},
 year = {2020},
 keywords = {T cell screening,frameshift mutations,neoantigens,neoepitopes,renal cell carcinoma},
 volume = {11},
 month = {3},
 publisher = {Frontiers Media S.A.},
 day = {12},
 id = {a27ddaca-c805-3c05-bd39-5269f4bad8cb},
 created = {2025-10-30T12:05:03.048Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:11.580Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Mutation-derived neoantigens are important targets for T cell-mediated reactivity toward tumors and, due to their unique tumor expression, an attractive target for immunotherapy. Neoepitope-specific T cells have been detected across a number of solid cancers with high mutational burden tumors, but neoepitopes have been mostly selected from single nucleotide variations (SNVs), and little focus has been given to neoepitopes derived from in-frame and frameshift indels, which might be equally important and potentially highly immunogenic. Clear cell renal cell carcinomas (ccRCCs) are medium-range mutational burden tumors with a high pan-cancer proportion of frameshift mutations. In this study, the mutational landscape of tumors from six RCC patients was analyzed by whole-exome sequencing (WES) of DNA from tumor fragments (TFs), autologous tumor cell lines (TCLs), and tumor-infiltrating lymphocytes (TILs, germline reference). Neopeptides were predicted using MuPeXI, and patient-specific peptide–MHC (pMHC) libraries were created for all neopeptides with a rank score < 2 for binding to the patient's HLAs. T cell recognition toward neoepitopes in TILs was evaluated using the high-throughput technology of DNA barcode-labeled pMHC multimers. The patient-specific libraries consisted of, on average, 258 putative neopeptides (range, 103–397, n = 6). In four patients, WES was performed on two different sources (TF and TCL), whereas in two patients, WES was performed only on TF. Most of the peptides were predicted from both sources. However, a fraction was predicted from one source only. Among the total predicted neopeptides, 16% were derived from frameshift indels. T cell recognition of 52 neoepitopes was detected across all patients (range, 4–18, n = 6) and spanning two to five HLA restrictions per patient. On average, 21% of the recognized neoepitopes were derived from frameshift indels (range, 0–43%, n = 6). Thus, frameshift indels are equally represented in the pool of immunogenic neoepitopes as SNV-derived neoepitopes. This suggests the importance of a broad neopeptide prediction strategy covering multiple sources of tumor material, and including different genetic alterations. This study, for the first time, describes the T cell recognition of frameshift-derived neoepitopes in RCC and determines their immunogenic profile.},
 bibtype = {article},
 author = {Hansen, Ulla Kring and Ramskov, Sofie and Bjerregaard, Anne Mette and Borch, Annie and Andersen, Rikke and Draghi, Arianna and Donia, Marco and Bentzen, Amalie Kai and Marquard, Andrea Marion and Szallasi, Zoltan and Eklund, Aron Charles and Svane, Inge Marie and Hadrup, Sine Reker},
 doi = {10.3389/FIMMU.2020.00373},
 journal = {Frontiers in Immunology}
}

Mutation-derived neoantigens are important targets for T cell-mediated reactivity toward tumors and, due to their unique tumor expression, an attractive target for immunotherapy. Neoepitope-specific T cells have been detected across a number of solid cancers with high mutational burden tumors, but neoepitopes have been mostly selected from single nucleotide variations (SNVs), and little focus has been given to neoepitopes derived from in-frame and frameshift indels, which might be equally important and potentially highly immunogenic. Clear cell renal cell carcinomas (ccRCCs) are medium-range mutational burden tumors with a high pan-cancer proportion of frameshift mutations. In this study, the mutational landscape of tumors from six RCC patients was analyzed by whole-exome sequencing (WES) of DNA from tumor fragments (TFs), autologous tumor cell lines (TCLs), and tumor-infiltrating lymphocytes (TILs, germline reference). Neopeptides were predicted using MuPeXI, and patient-specific peptide–MHC (pMHC) libraries were created for all neopeptides with a rank score < 2 for binding to the patient's HLAs. T cell recognition toward neoepitopes in TILs was evaluated using the high-throughput technology of DNA barcode-labeled pMHC multimers. The patient-specific libraries consisted of, on average, 258 putative neopeptides (range, 103–397, n = 6). In four patients, WES was performed on two different sources (TF and TCL), whereas in two patients, WES was performed only on TF. Most of the peptides were predicted from both sources. However, a fraction was predicted from one source only. Among the total predicted neopeptides, 16% were derived from frameshift indels. T cell recognition of 52 neoepitopes was detected across all patients (range, 4–18, n = 6) and spanning two to five HLA restrictions per patient. On average, 21% of the recognized neoepitopes were derived from frameshift indels (range, 0–43%, n = 6). Thus, frameshift indels are equally represented in the pool of immunogenic neoepitopes as SNV-derived neoepitopes. This suggests the importance of a broad neopeptide prediction strategy covering multiple sources of tumor material, and including different genetic alterations. This study, for the first time, describes the T cell recognition of frameshift-derived neoepitopes in RCC and determines their immunogenic profile.

@article{
 title = {The intestinal microbiome is a co-determinant of the postprandial plasma glucose response},
 type = {article},
 year = {2020},
 volume = {15},
 month = {9},
 publisher = {Public Library of Science},
 day = {1},
 id = {35bfb9ec-1d8b-33d3-ac77-c685f3d3e323},
 created = {2025-10-30T12:05:03.077Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:11.325Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Elevated postprandial plasma glucose is a risk factor for development of type 2 diabetes and cardiovascular disease. We hypothesized that the inter-individual postprandial plasma glucose response varies partly depending on the intestinal microbiome composition and function. We analyzed data from Danish adults (n = 106), who were self-reported healthy and attended the baseline visit of two previously reported randomized controlled cross-over trials within the Gut, Grain and Greens project. Plasma glucose concentrations at five time points were measured before and during three hours after a standardized breakfast. Based on these data, we devised machine learning algorithms integrating bio-clinical, as well as shotgun-sequencing-derived taxa and functional potentials of the intestinal microbiome to predict individual postprandial glucose excursions. In this post hoc study, we found microbial and clinical features, which predicted up to 48% of the inter-individual variance of postprandial plasma glucose responses (Pearson correlation coefficient of measured vs. predicted values, R = 0.69, 95% CI: 0.45 to 0.84, p<0.001). The features were age, fasting serum triglycerides, systolic blood pressure, BMI, fasting total serum cholesterol, abundance of Bifidobacterium genus, richness of metagenomics species and abundance of a metagenomic species annotated to Clostridiales at order level. A model based only on microbial features predicted up to 14% of the variance in postprandial plasma glucose excursions (R = 0.37, 95% CI: 0.02 to 0.64, p = 0.04). Adding fasting glycaemic measures to the model including microbial and bio-clinical features increased the predictive power to R = 0.78 (95% CI: 0.59 to 0.89, p<0.001), explaining more than 60% of the inter-individual variance of postprandial plasma glucose concentrations. The outcome of the study points to a potential role of the taxa and functional potentials of the intestinal microbiome. If validated in larger studies our findings may be included in future algorithms attempting to develop personalized nutrition, especially for prediction of individual blood glucose excursions in dys-glycaemic individuals.},
 bibtype = {article},
 author = {Søndertoft, Nadja B. and Vogt, Josef K. and Arumugam, Manimozhiyan and Kristensen, Mette and Gøbel, Rikke J. and Fan, Yong and Lyu, Liwei and Bahl, Martin I. and Eriksen, Carsten and Ängquist, Lars and Frøkiær, Hanne and Hansen, Tue H. and Brix, Susanne and Bjørn Nielsen, H. and Hansen, Torben and Vestergaard, Henrik and Gupta, Ramneek and Licht, Tine R. and Lauritzen, Lotte and Pedersen, Oluf},
 doi = {10.1371/JOURNAL.PONE.0238648},
 journal = {PLoS ONE},
 number = {9 September}
}

Elevated postprandial plasma glucose is a risk factor for development of type 2 diabetes and cardiovascular disease. We hypothesized that the inter-individual postprandial plasma glucose response varies partly depending on the intestinal microbiome composition and function. We analyzed data from Danish adults (n = 106), who were self-reported healthy and attended the baseline visit of two previously reported randomized controlled cross-over trials within the Gut, Grain and Greens project. Plasma glucose concentrations at five time points were measured before and during three hours after a standardized breakfast. Based on these data, we devised machine learning algorithms integrating bio-clinical, as well as shotgun-sequencing-derived taxa and functional potentials of the intestinal microbiome to predict individual postprandial glucose excursions. In this post hoc study, we found microbial and clinical features, which predicted up to 48% of the inter-individual variance of postprandial plasma glucose responses (Pearson correlation coefficient of measured vs. predicted values, R = 0.69, 95% CI: 0.45 to 0.84, p<0.001). The features were age, fasting serum triglycerides, systolic blood pressure, BMI, fasting total serum cholesterol, abundance of Bifidobacterium genus, richness of metagenomics species and abundance of a metagenomic species annotated to Clostridiales at order level. A model based only on microbial features predicted up to 14% of the variance in postprandial plasma glucose excursions (R = 0.37, 95% CI: 0.02 to 0.64, p = 0.04). Adding fasting glycaemic measures to the model including microbial and bio-clinical features increased the predictive power to R = 0.78 (95% CI: 0.59 to 0.89, p<0.001), explaining more than 60% of the inter-individual variance of postprandial plasma glucose concentrations. The outcome of the study points to a potential role of the taxa and functional potentials of the intestinal microbiome. If validated in larger studies our findings may be included in future algorithms attempting to develop personalized nutrition, especially for prediction of individual blood glucose excursions in dys-glycaemic individuals.

@article{
 title = {High abundance of proteobacteria in ileo-anal pouch anastomosis and increased abundance of fusobacteria associated with increased pouch inflammation},
 type = {article},
 year = {2020},
 keywords = {Calprotectin,Escherichia coli,Fusobacteria,Inflammatory bowel disease,Pouchitis,Proteobacteria},
 volume = {9},
 month = {5},
 publisher = {MDPI AG},
 day = {1},
 id = {27af320b-b5c3-3d77-ae8a-18ddb75aebf5},
 created = {2025-10-30T12:05:03.087Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:05:11.041Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Low diversity intestinal dysbiosis has been associated with inflammatory bowel disease, including patients with ulcerative colitis with an ileo-anal pouch anastomosis. Furthermore, specific Escherichia coli phylogroups have been linked to inflammatory bowel disease. Our aim was to characterize the differences among microbiota and E. coli phylogroups in active and inactive pouchitis. Disease activity was assessed using the modified pouch disease activity index and by fecal calprotectin. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. E. coli phylogroup was determined after triplex PCR. Twenty patients with ulcerative colitis with an ileo-anal pouch anastomosis were included, 10 of whom had active pouchitis. Ileo-anal pouch anastomosis patients had an increased abundance of Proteobacteria colonization compared to patients with ulcerative colitis or Crohn’s disease and healthy controls, p = 1.4·10−5. No differences in E. coli phylogroup colonization could be determined between cases of active and inactive disease. No significant link was found between α-diversity and pouch inflammation. However, higher levels of Fusobacteria colonization were found in patients with a pouch with a fecal calprotectin level above 500, p = 0.02. In conclusion, patients with a pouch had an increased Proteobacteria abundance, but only Fusobacteria abundance was linked to inflammation.},
 bibtype = {article},
 author = {Petersen, Andreas Munk and Mirsepasi-Lauridsen, Hengameh Chloé and Vester-Andersen, Marianne K. and Sørensen, Nikolaj and Krogfelt, Karen Angeliki and Bendtsen, Flemming},
 doi = {10.3390/ANTIBIOTICS9050237},
 journal = {Antibiotics},
 number = {5}
}

Low diversity intestinal dysbiosis has been associated with inflammatory bowel disease, including patients with ulcerative colitis with an ileo-anal pouch anastomosis. Furthermore, specific Escherichia coli phylogroups have been linked to inflammatory bowel disease. Our aim was to characterize the differences among microbiota and E. coli phylogroups in active and inactive pouchitis. Disease activity was assessed using the modified pouch disease activity index and by fecal calprotectin. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. E. coli phylogroup was determined after triplex PCR. Twenty patients with ulcerative colitis with an ileo-anal pouch anastomosis were included, 10 of whom had active pouchitis. Ileo-anal pouch anastomosis patients had an increased abundance of Proteobacteria colonization compared to patients with ulcerative colitis or Crohn’s disease and healthy controls, p = 1.4·10−5. No differences in E. coli phylogroup colonization could be determined between cases of active and inactive disease. No significant link was found between α-diversity and pouch inflammation. However, higher levels of Fusobacteria colonization were found in patients with a pouch with a fecal calprotectin level above 500, p = 0.02. In conclusion, patients with a pouch had an increased Proteobacteria abundance, but only Fusobacteria abundance was linked to inflammation.

@article{
 title = {Interventional Influence of the Intestinal Microbiome Through Dietary Intervention and Bowel Cleansing Might Improve Motor Symptoms in Parkinson's Disease},
 type = {article},
 year = {2020},
 keywords = {Parkinson’s disease,butyric acid,enema,microbiome,vegetarian diet},
 volume = {9},
 month = {2},
 publisher = {NLM (Medline)},
 day = {6},
 id = {ebe2fb32-d1bb-377b-b87f-c816e71b9a54},
 created = {2025-10-30T12:09:26.820Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:29.361Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson's disease (PD). In the pathogenesis of PD, the role of the gut has been previously established. In conjunction with a better understanding of the intestinal microbiome, a link to the misfolding and spread of alpha-synuclein via inflammatory processes within the gut is discussed. In a case-control study, we assessed the gut microbiome of 54 PD patients and 32 healthy controls (HC). Additionally, we tested in this proof-of-concept study whether dietary intervention alone or additional physical colon cleaning may lead to changes of the gut microbiome in PD. 16 PD patients underwent a well-controlled balanced, ovo-lacto vegetarian diet intervention including short fatty acids for 14 days. 10 of those patients received additional treatment with daily fecal enema over 8 days. Stool samples were collected before and after 14 days of intervention. In comparison to HC, we could confirm previously reported PD associated microbiome changes. The UDPRS III significantly improved and the levodopa-equivalent daily dose decreased after vegetarian diet and fecal enema in a one-year follow-up. Additionally, we observed a significant association between the gut microbiome diversity and the UPDRS III and the abundance of Ruminococcaceae. Additionally, the abundance of Clostridiaceae was significantly reduced after enema. Dietary intervention and bowel cleansing may provide an additional non-pharmacologic therapeutic option for PD patients.},
 bibtype = {article},
 author = {Hegelmaier, Tobias and Lebbing, Marco and Duscha, Alexander and Tomaske, Laura and Tönges, Lars and Holm, Jacob Bak and Bjørn Nielsen, Henrik and Gatermann, Sören G. and Przuntek, Horst and Haghikia, Aiden},
 doi = {10.3390/cells9020376},
 journal = {Cells},
 number = {2}
}

The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson's disease (PD). In the pathogenesis of PD, the role of the gut has been previously established. In conjunction with a better understanding of the intestinal microbiome, a link to the misfolding and spread of alpha-synuclein via inflammatory processes within the gut is discussed. In a case-control study, we assessed the gut microbiome of 54 PD patients and 32 healthy controls (HC). Additionally, we tested in this proof-of-concept study whether dietary intervention alone or additional physical colon cleaning may lead to changes of the gut microbiome in PD. 16 PD patients underwent a well-controlled balanced, ovo-lacto vegetarian diet intervention including short fatty acids for 14 days. 10 of those patients received additional treatment with daily fecal enema over 8 days. Stool samples were collected before and after 14 days of intervention. In comparison to HC, we could confirm previously reported PD associated microbiome changes. The UDPRS III significantly improved and the levodopa-equivalent daily dose decreased after vegetarian diet and fecal enema in a one-year follow-up. Additionally, we observed a significant association between the gut microbiome diversity and the UPDRS III and the abundance of Ruminococcaceae. Additionally, the abundance of Clostridiaceae was significantly reduced after enema. Dietary intervention and bowel cleansing may provide an additional non-pharmacologic therapeutic option for PD patients.

@article{
 title = {Similar genomic patterns of clinical infective endocarditis and oral isolates of Streptococcus sanguinis and Streptococcus gordonii},
 type = {article},
 year = {2020},
 volume = {10},
 month = {12},
 publisher = {Nature Research},
 day = {1},
 id = {a4c668b2-349c-3d6d-86c7-ff3b533236df},
 created = {2025-10-30T12:09:26.840Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:30.392Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Streptococcus gordonii and Streptococcus sanguinis belong to the Mitis group streptococci, which mostly are commensals in the human oral cavity. Though they are oral commensals, they can escape their niche and cause infective endocarditis, a severe infection with high mortality. Several virulence factors important for the development of infective endocarditis have been described in these two species. However, the background for how the commensal bacteria, in some cases, become pathogenic is still not known. To gain a greater understanding of the mechanisms of the pathogenic potential, we performed a comparative analysis of 38 blood culture strains, S. sanguinis (n = 20) and S. gordonii (n = 18) from patients with verified infective endocarditis, along with 21 publicly available oral isolates from healthy individuals, S. sanguinis (n = 12) and S. gordonii (n = 9). Using whole genome sequencing data of the 59 streptococci genomes, functional profiles were constructed, using protein domain predictions based on the translated genes. These functional profiles were used for clustering, phylogenetics and machine learning. A clear separation could be made between the two species. No clear differences between oral isolates and clinical infective endocarditis isolates were found in any of the 675 translated core-genes. Additionally, random forest-based machine learning and clustering of the pan-genome data as well as amino acid variations in the core-genome could not separate the clinical and oral isolates. A total of 151 different virulence genes was identified in the 59 genomes. Among these homologs of genes important for adhesion and evasion of the immune system were found in all of the strains. Based on the functional profiles and virulence gene content of the genomes, we believe that all analysed strains had the ability to become pathogenic.},
 bibtype = {article},
 author = {Iversen, Katrine Højholt and Rasmussen, Louise Hesselbjerg and Al-Nakeeb, Kosai and Armenteros, Jose Juan Almagro and Jensen, Christian Salgård and Dargis, Rimtas and Lukjancenko, Oksana and Justesen, Ulrik Stenz and Moser, Claus and Rosenvinge, Flemming S. and Nielsen, Xiaohui Chen and Christensen, Jens Jørgen and Rasmussen, Simon},
 doi = {10.1038/s41598-020-59549-4},
 journal = {Scientific Reports},
 number = {1}
}

Streptococcus gordonii and Streptococcus sanguinis belong to the Mitis group streptococci, which mostly are commensals in the human oral cavity. Though they are oral commensals, they can escape their niche and cause infective endocarditis, a severe infection with high mortality. Several virulence factors important for the development of infective endocarditis have been described in these two species. However, the background for how the commensal bacteria, in some cases, become pathogenic is still not known. To gain a greater understanding of the mechanisms of the pathogenic potential, we performed a comparative analysis of 38 blood culture strains, S. sanguinis (n = 20) and S. gordonii (n = 18) from patients with verified infective endocarditis, along with 21 publicly available oral isolates from healthy individuals, S. sanguinis (n = 12) and S. gordonii (n = 9). Using whole genome sequencing data of the 59 streptococci genomes, functional profiles were constructed, using protein domain predictions based on the translated genes. These functional profiles were used for clustering, phylogenetics and machine learning. A clear separation could be made between the two species. No clear differences between oral isolates and clinical infective endocarditis isolates were found in any of the 675 translated core-genes. Additionally, random forest-based machine learning and clustering of the pan-genome data as well as amino acid variations in the core-genome could not separate the clinical and oral isolates. A total of 151 different virulence genes was identified in the 59 genomes. Among these homologs of genes important for adhesion and evasion of the immune system were found in all of the strains. Based on the functional profiles and virulence gene content of the genomes, we believe that all analysed strains had the ability to become pathogenic.

@article{
 title = {Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism},
 type = {article},
 year = {2020},
 keywords = {autoimmune diseases,immune modulation,microbiome,multiple sclerosis,neuroregeneration,propionic acid,regulatory T cells},
 pages = {1067-1080.e16},
 volume = {180},
 month = {3},
 publisher = {Elsevier B.V.},
 day = {19},
 id = {5bc9ddb3-0e6e-35b0-8b4c-0de83b2c17ef},
 created = {2025-10-30T12:09:26.860Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:30.459Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Short-chain fatty acids are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here, we investigate propionic acid (PA) in multiple sclerosis (MS), an autoimmune and neurodegenerative disease. Serum and feces of subjects with MS exhibited significantly reduced PA amounts compared with controls, particularly after the first relapse. In a proof-of-concept study, we supplemented PA to therapy-naive MS patients and as an add-on to MS immunotherapy. After 2 weeks of PA intake, we observed a significant and sustained increase of functionally competent regulatory T (Treg) cells, whereas Th1 and Th17 cells decreased significantly. Post-hoc analyses revealed a reduced annual relapse rate, disability stabilization, and reduced brain atrophy after 3 years of PA intake. Functional microbiome analysis revealed increased expression of Treg-cell-inducing genes in the intestine after PA intake. Furthermore, PA normalized Treg cell mitochondrial function and morphology in MS. Our findings suggest that PA can serve as a potent immunomodulatory supplement to MS drugs.},
 bibtype = {article},
 author = {Duscha, Alexander and Gisevius, Barbara and Hirschberg, Sarah and Yissachar, Nissan and Stangl, Gabriele I. and Dawin, Eva and Bader, Verian and Haase, Stefanie and Kaisler, Johannes and David, Christina and Schneider, Ruth and Troisi, Riccardo and Zent, Daniel and Hegelmaier, Tobias and Dokalis, Nikolaos and Gerstein, Sara and Del Mare-Roumani, Sara and Amidror, Sivan and Staszewski, Ori and Poschmann, Gereon and Stühler, Kai and Hirche, Frank and Balogh, Andras and Kempa, Stefan and Träger, Pascal and Zaiss, Mario M. and Holm, Jacob Bak and Massa, Megan G. and Nielsen, Henrik Bjørn and Faissner, Andreas and Lukas, Carsten and Gatermann, Sören G. and Scholz, Markus and Przuntek, Horst and Prinz, Marco and Forslund, Sofia K. and Winklhofer, Konstanze F. and Müller, Dominik N. and Linker, Ralf A. and Gold, Ralf and Haghikia, Aiden},
 doi = {10.1016/j.cell.2020.02.035},
 journal = {Cell},
 number = {6}
}

Short-chain fatty acids are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here, we investigate propionic acid (PA) in multiple sclerosis (MS), an autoimmune and neurodegenerative disease. Serum and feces of subjects with MS exhibited significantly reduced PA amounts compared with controls, particularly after the first relapse. In a proof-of-concept study, we supplemented PA to therapy-naive MS patients and as an add-on to MS immunotherapy. After 2 weeks of PA intake, we observed a significant and sustained increase of functionally competent regulatory T (Treg) cells, whereas Th1 and Th17 cells decreased significantly. Post-hoc analyses revealed a reduced annual relapse rate, disability stabilization, and reduced brain atrophy after 3 years of PA intake. Functional microbiome analysis revealed increased expression of Treg-cell-inducing genes in the intestine after PA intake. Furthermore, PA normalized Treg cell mitochondrial function and morphology in MS. Our findings suggest that PA can serve as a potent immunomodulatory supplement to MS drugs.

@article{
 title = {A comparative analysis of drinking water employing metagenomics},
 type = {article},
 year = {2020},
 volume = {15},
 month = {4},
 publisher = {Public Library of Science},
 day = {1},
 id = {39fdd981-65e7-3d93-952a-0070d8459004},
 created = {2025-10-30T12:26:00.959Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:09.707Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The microbiological content of drinking water traditionally is determined by employing culture- dependent methods that are unable to detect all microorganisms, especially those that are not culturable. High-throughput sequencing now makes it possible to determine the microbiome of drinking water. Thus, the natural microbiota of water and water distribution systems can now be determined more accurately and analyzed in significantly greater detail, providing comprehensive understanding of the microbial community of drinking water applicable to public health. In this study, shotgun metagenomic analysis was performed to determine the microbiological content of drinking water and to provide a preliminary assessment of tap, drinking fountain, sparkling natural mineral, and non-mineral bottled water. Predominant bacterial species detected were members of the phyla Actinobacteria and Proteobacteria, notably the genera Alishewanella, Salmonella, and Propionibacterium in non-carbonated non-mineral bottled water, Methyloversatilis and Methylibium in sparkling natural mineral water, and Mycobacterium and Afipia in tap and drinking fountain water. Fecal indicator bacteria, i.e., Escherichia coli or enterococci, were not detected in any samples examined in this study. Bacteriophages and DNA encoding a few virulence-associated factors were detected but determined to be present only at low abundance. Antibiotic resistance markers were detected only at abundance values below our threshold of confidence. DNA of opportunistic plant and animal pathogens was identified in some samples and these included bacteria (Mycobacterium spp.), protozoa (Acanthamoeba mauritaniensis and Acanthamoeba palestinensis), and fungi (Melampsora pinitorqua and Chryosporium queenslandicum). Archaeal DNA (Candidatus Nitrosoarchaeum) was detected only in sparkling natural mineral water. This preliminary study reports the complete microbiome (bacteria, viruses, fungi, and protists) of selected types of drinking water employing whole-genome high-throughput sequencing and bioinformatics. Investigation into activity and function of the organisms detected is in progress.},
 bibtype = {article},
 author = {Brumfield, Kyle D. and Hasan, Nur A. and Leddy, Menu B. and Cotruvo, Joseph A. and Rashed, Shah M. and Colwell, Rita R. and Huq, Anwar},
 doi = {10.1371/JOURNAL.PONE.0231210},
 journal = {PLoS ONE},
 number = {4}
}

The microbiological content of drinking water traditionally is determined by employing culture- dependent methods that are unable to detect all microorganisms, especially those that are not culturable. High-throughput sequencing now makes it possible to determine the microbiome of drinking water. Thus, the natural microbiota of water and water distribution systems can now be determined more accurately and analyzed in significantly greater detail, providing comprehensive understanding of the microbial community of drinking water applicable to public health. In this study, shotgun metagenomic analysis was performed to determine the microbiological content of drinking water and to provide a preliminary assessment of tap, drinking fountain, sparkling natural mineral, and non-mineral bottled water. Predominant bacterial species detected were members of the phyla Actinobacteria and Proteobacteria, notably the genera Alishewanella, Salmonella, and Propionibacterium in non-carbonated non-mineral bottled water, Methyloversatilis and Methylibium in sparkling natural mineral water, and Mycobacterium and Afipia in tap and drinking fountain water. Fecal indicator bacteria, i.e., Escherichia coli or enterococci, were not detected in any samples examined in this study. Bacteriophages and DNA encoding a few virulence-associated factors were detected but determined to be present only at low abundance. Antibiotic resistance markers were detected only at abundance values below our threshold of confidence. DNA of opportunistic plant and animal pathogens was identified in some samples and these included bacteria (Mycobacterium spp.), protozoa (Acanthamoeba mauritaniensis and Acanthamoeba palestinensis), and fungi (Melampsora pinitorqua and Chryosporium queenslandicum). Archaeal DNA (Candidatus Nitrosoarchaeum) was detected only in sparkling natural mineral water. This preliminary study reports the complete microbiome (bacteria, viruses, fungi, and protists) of selected types of drinking water employing whole-genome high-throughput sequencing and bioinformatics. Investigation into activity and function of the organisms detected is in progress.

@article{
 title = {Multiple NDM-5-expressing Escherichia coli isolates from an immunocompromised pediatric host},
 type = {article},
 year = {2020},
 keywords = {Immunocompromised,Multidrug-resistant,NDM-5,Pediatric},
 volume = {7},
 month = {2},
 publisher = {Oxford University Press},
 day = {1},
 id = {916d1143-24a3-3faf-94b5-85fec4d9ad70},
 created = {2025-10-30T12:26:00.960Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:23.236Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background. Genes conferring carbapenem resistance have disseminated worldwide among Gram-negative bacteria. Here we present longitudinal changes in clinically obtained Escherichia coli isolates from 1 immunocompromised pediatric patient. This report demonstrates potential for antibiotic resistance genes and plasmids to emerge over time in clinical isolates from patients receiving intensive anticancer chemotherapy and broad-spectrum antibiotics. Methods. Thirty-three isolates obtained over 7 months from 1 patient were included. Clinical data were abstracted from the medical record. For each isolate, studies included phenotypic antibacterial resistance patterns, sequence typing, bacterial isolate sequencing, plasmid identification, and antibiotic resistance gene identification. Results. Sites of isolation included blood, wound culture, and culture for surveillance purposes from the perianal area. Isolates were of 5 sequence types (STs). All were resistant to multiple classes of antibiotics; 23 (69.6%) were phenotypically resistant to all carbapenems. The blaNDM-5 gene was identified in 22 (67%) isolates, all of ST-167 and ST-940, and appeared to coincide with the presence of the IncFII and IncX3 plasmid. Conclusions. We present unique microbiologic data from 33 multidrug-resistant E. coli isolates obtained over the course of 7 months from an individual patient in the United States. Two E. coli sequence types causing invasive infection in the same patient and harboring the blaNDM-5 gene, encoded on the IncX3 plasmid and the IncFII plasmid, were identified. This study highlights the emergence of multidrug-resistant bacteria on antibiotic therapy and the necessity of adequate neutrophil number and function in the clearance of bacteremia.},
 bibtype = {article},
 author = {Flerlage, Tim and Brazelton de Cardenas, Jessica N. and Garner, Cherilyn D. and Hasan, Nur A. and Karathia, Hiren and Qudeimat, Amr and Maron, Gabriela and Hayden, Randall},
 doi = {10.1093/OFID/OFAA018},
 journal = {Open Forum Infectious Diseases},
 number = {2}
}

Background. Genes conferring carbapenem resistance have disseminated worldwide among Gram-negative bacteria. Here we present longitudinal changes in clinically obtained Escherichia coli isolates from 1 immunocompromised pediatric patient. This report demonstrates potential for antibiotic resistance genes and plasmids to emerge over time in clinical isolates from patients receiving intensive anticancer chemotherapy and broad-spectrum antibiotics. Methods. Thirty-three isolates obtained over 7 months from 1 patient were included. Clinical data were abstracted from the medical record. For each isolate, studies included phenotypic antibacterial resistance patterns, sequence typing, bacterial isolate sequencing, plasmid identification, and antibiotic resistance gene identification. Results. Sites of isolation included blood, wound culture, and culture for surveillance purposes from the perianal area. Isolates were of 5 sequence types (STs). All were resistant to multiple classes of antibiotics; 23 (69.6%) were phenotypically resistant to all carbapenems. The blaNDM-5 gene was identified in 22 (67%) isolates, all of ST-167 and ST-940, and appeared to coincide with the presence of the IncFII and IncX3 plasmid. Conclusions. We present unique microbiologic data from 33 multidrug-resistant E. coli isolates obtained over the course of 7 months from an individual patient in the United States. Two E. coli sequence types causing invasive infection in the same patient and harboring the blaNDM-5 gene, encoded on the IncX3 plasmid and the IncFII plasmid, were identified. This study highlights the emergence of multidrug-resistant bacteria on antibiotic therapy and the necessity of adequate neutrophil number and function in the clearance of bacteremia.

@article{
 title = {Metagenomic next-generation sequencing of nasopharyngeal specimens collected from confirmed and suspect covid-19 patients},
 type = {article},
 year = {2020},
 keywords = {COVID-19,Metagenomic next-generation sequencing,Metagenomics,Nasopharyngeal,SARS-CoV-2},
 pages = {1-13},
 volume = {11},
 month = {11},
 publisher = {American Society for Microbiology},
 day = {1},
 id = {659a00bf-e1f8-343e-8a68-b8ab4a79690c},
 created = {2025-10-30T12:26:00.973Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:25.295Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Metagenomic next-generation sequencing (mNGS) offers an agnostic approach for emerging pathogen detection directly from clinical specimens. In con-trast to targeted methods, mNGS also provides valuable information on the composition of the microbiome and might uncover coinfections that may associate with disease progression and impact prognosis. To evaluate the use of mNGS for detect-ing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or other in-fecting pathogens, we applied direct Oxford Nanopore long-read third-generation metatranscriptomic and metagenomic sequencing. Nasopharyngeal (NP) swab specimens from 50 patients under investigation for CoV disease 2019 (COVID-19) were se-quenced, and the data were analyzed by the CosmosID bioinformatics platform. Fur-ther, we characterized coinfections and the microbiome associated with a four-point severity index. SARS-CoV-2 was identified in 77.5% (31/40) of samples positive by RT-PCR, correlating with lower cycle threshold (Ct) values and fewer days from symp-tom onset. At the time of sampling, possible bacterial or viral coinfections were detected in 12.5% of SARS-CoV-2-positive specimens. A decrease in microbial diversity was observed among COVID-19-confirmed patients (Shannon diversity index, P = 0.0082; Chao richness estimate, P = 0.0097; Simpson diversity index, P = 0.018), and differences in microbial communities were linked to disease severity (P = 0.022). Furthermore, statistically significant shifts in the microbiome were identified among SARS-CoV-2-positive and-negative patients, in the latter of whom a higher abundance of Propionibacteriaceae (P = 0.028) and a reduction in the abundance of Co-rynebacterium accolens (P = 0.025) were observed. Our study corroborates the growing evidence that increased SARS-CoV-2 RNA detection from NP swabs is associated with the early stages rather than the severity of COVID-19. Further, we demonstrate that SARS-CoV-2 causes a significant change in the respiratory microbiome. This work illustrates the utility of mNGS for the detection of SARS-CoV-2, for diagnosing coinfections without viral target enrichment or amplification, and for the analysis of the respiratory microbiome. IMPORTANCE SARS-CoV-2 has presented a rapidly accelerating global public health crisis. The ability to detect and analyze viral RNA from minimally invasive patient specimens is critical to the public health response. Metagenomic next-generation sequencing (mNGS) offers an opportunity to detect SARS-CoV-2 from nasopharyngeal (NP) swabs. This approach also provides information on the composition of the respiratory microbiome and its relationship to coinfections or the presence of other organisms that may impact SARS-CoV-2 disease progression and prognosis. Here, using direct Oxford Nanopore long-read third-generation metatranscriptomic and met-agenomic sequencing of NP swab specimens from 50 patients under investigation for COVID-19, we detected SARS-CoV-2 sequences by applying the CosmosID bioin-formatics platform. Further, we characterized coinfections and detected a decrease in the diversity of the microbiomes in these patients. Statistically significant shifts in the microbiome were identified among COVID-19-positive and-negative patients, in the latter of whom a higher abundance of Propionibacteriaceae and a reduction in the abundance of Corynebacterium accolens were observed. Our study also corroborates the growing evidence that increased SARS-CoV-2 RNA detection from NP swabs is associated with the early stages of disease rather than with severity of dis-ease. This work illustrates the utility of mNGS for the detection and analysis of SARS-CoV-2 from NP swabs without viral target enrichment or amplification and for the analysis of the respiratory microbiome.},
 bibtype = {article},
 author = {Mostafa, Heba H. and Fissel, John A. and Fanelli, Brian and Bergman, Yehudit and Gniazdowski, Victoria and Dadlani, Manoj and Carroll, Karen C. and Colwell, Rita R. and Simner, Patricia J.},
 doi = {10.1128/MBIO.01969-20},
 journal = {mBio},
 number = {6}
}

Metagenomic next-generation sequencing (mNGS) offers an agnostic approach for emerging pathogen detection directly from clinical specimens. In con-trast to targeted methods, mNGS also provides valuable information on the composition of the microbiome and might uncover coinfections that may associate with disease progression and impact prognosis. To evaluate the use of mNGS for detect-ing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or other in-fecting pathogens, we applied direct Oxford Nanopore long-read third-generation metatranscriptomic and metagenomic sequencing. Nasopharyngeal (NP) swab specimens from 50 patients under investigation for CoV disease 2019 (COVID-19) were se-quenced, and the data were analyzed by the CosmosID bioinformatics platform. Fur-ther, we characterized coinfections and the microbiome associated with a four-point severity index. SARS-CoV-2 was identified in 77.5% (31/40) of samples positive by RT-PCR, correlating with lower cycle threshold (Ct) values and fewer days from symp-tom onset. At the time of sampling, possible bacterial or viral coinfections were detected in 12.5% of SARS-CoV-2-positive specimens. A decrease in microbial diversity was observed among COVID-19-confirmed patients (Shannon diversity index, P = 0.0082; Chao richness estimate, P = 0.0097; Simpson diversity index, P = 0.018), and differences in microbial communities were linked to disease severity (P = 0.022). Furthermore, statistically significant shifts in the microbiome were identified among SARS-CoV-2-positive and-negative patients, in the latter of whom a higher abundance of Propionibacteriaceae (P = 0.028) and a reduction in the abundance of Co-rynebacterium accolens (P = 0.025) were observed. Our study corroborates the growing evidence that increased SARS-CoV-2 RNA detection from NP swabs is associated with the early stages rather than the severity of COVID-19. Further, we demonstrate that SARS-CoV-2 causes a significant change in the respiratory microbiome. This work illustrates the utility of mNGS for the detection of SARS-CoV-2, for diagnosing coinfections without viral target enrichment or amplification, and for the analysis of the respiratory microbiome. IMPORTANCE SARS-CoV-2 has presented a rapidly accelerating global public health crisis. The ability to detect and analyze viral RNA from minimally invasive patient specimens is critical to the public health response. Metagenomic next-generation sequencing (mNGS) offers an opportunity to detect SARS-CoV-2 from nasopharyngeal (NP) swabs. This approach also provides information on the composition of the respiratory microbiome and its relationship to coinfections or the presence of other organisms that may impact SARS-CoV-2 disease progression and prognosis. Here, using direct Oxford Nanopore long-read third-generation metatranscriptomic and met-agenomic sequencing of NP swab specimens from 50 patients under investigation for COVID-19, we detected SARS-CoV-2 sequences by applying the CosmosID bioin-formatics platform. Further, we characterized coinfections and detected a decrease in the diversity of the microbiomes in these patients. Statistically significant shifts in the microbiome were identified among COVID-19-positive and-negative patients, in the latter of whom a higher abundance of Propionibacteriaceae and a reduction in the abundance of Corynebacterium accolens were observed. Our study also corroborates the growing evidence that increased SARS-CoV-2 RNA detection from NP swabs is associated with the early stages of disease rather than with severity of dis-ease. This work illustrates the utility of mNGS for the detection and analysis of SARS-CoV-2 from NP swabs without viral target enrichment or amplification and for the analysis of the respiratory microbiome.

@article{
 title = {Multi-omics analysis reveals the influence of genetic and environmental risk factors on developing gut microbiota in infants at risk of celiac disease},
 type = {article},
 year = {2020},
 keywords = {Celiac disease,Microbiota,Multi-omics analysis, gut microbiome},
 volume = {8},
 month = {9},
 publisher = {BioMed Central Ltd},
 day = {11},
 id = {e8bcd83f-1123-32bf-9b49-ed512ebd93ca},
 created = {2025-10-30T12:26:00.992Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:27:46.577Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Celiac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals in response to ingesting gluten, a protein found in wheat, rye, and barley. Research shows that genetic predisposition and exposure to gluten are necessary but not sufficient to trigger the development of CD. This suggests that exposure to other environmental stimuli early in life, e.g., cesarean section delivery and exposure to antibiotics or formula feeding, may also play a key role in CD pathogenesis through yet unknown mechanisms. Here, we use multi-omics analysis to investigate how genetic and early environmental risk factors alter the development of the gut microbiota in infants at risk of CD. Results: Toward this end, we selected 31 infants from a large-scale prospective birth cohort study of infants with a first-degree relative with CD. We then performed rigorous multivariate association, cross-sectional, and longitudinal analyses using metagenomic and metabolomic data collected at birth, 3 months and 6 months of age to explore the impact of genetic predisposition and environmental risk factors on the gut microbiota composition, function, and metabolome prior to the introduction of trigger (gluten). These analyses revealed several microbial species, functional pathways, and metabolites that are associated with each genetic and environmental risk factor or that are differentially abundant between environmentally exposed and non-exposed infants or between time points. Among our significant findings, we found that cesarean section delivery is associated with a decreased abundance of Bacteroides vulgatus and Bacteroides dorei and of folate biosynthesis pathway and with an increased abundance of hydroxyphenylacetic acid, alterations that are implicated in immune system dysfunction and inflammatory conditions. Additionally, longitudinal analysis revealed that, in infants not exposed to any environmental risk factor, the abundances of Bacteroides uniformis and of metabolite 3-3-hydroxyphenylproprionic acid increase over time, while those for lipoic acid and methane metabolism pathways decrease, patterns that are linked to beneficial immunomodulatory and anti-inflammatory effects. Conclusions: Overall, our study provides unprecedented insights into major taxonomic and functional shifts in the developing gut microbiota of infants at risk of CD linking genetic and environmental risk factors to detrimental immunomodulatory and inflammatory effects. [MediaObject not available: see fulltext.].},
 bibtype = {article},
 author = {Leonard, Maureen M. and Karathia, Hiren and Pujolassos, Meritxell and Troisi, Jacopo and Valitutti, Francesco and Subramanian, Poorani and Camhi, Stephanie and Kenyon, Victoria and Colucci, Angelo and Serena, Gloria and Cucchiara, Salvatore and Montuori, Monica and Malamisura, Basilio and Francavilla, Ruggiero and Elli, Luca and Fanelli, Brian and Colwell, Rita and Hasan, Nur and Zomorrodi, Ali R. and Fasano, Alessio and Piemontese, Pasqua and Calvi, Angela and Baldassarre, Mariella and Norsa, Lorenzo and Trovato, Chiara Maria and Raguseo, Celeste Lidia and Passaro, Tiziana and Roggero, Paola and Crocco, Marco and Morelli, Annalisa and Perrone, Michela and Chieppa, Marcello and Scala, Giovanni and Lionetti, Maria Elena and Catassi, Carlo and Serretiello, Adelaide and Vecchi, Corrado and De Villsante, Gemma Castillejo},
 doi = {10.1186/S40168-020-00906-W},
 journal = {Microbiome},
 number = {1}
}

Background: Celiac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals in response to ingesting gluten, a protein found in wheat, rye, and barley. Research shows that genetic predisposition and exposure to gluten are necessary but not sufficient to trigger the development of CD. This suggests that exposure to other environmental stimuli early in life, e.g., cesarean section delivery and exposure to antibiotics or formula feeding, may also play a key role in CD pathogenesis through yet unknown mechanisms. Here, we use multi-omics analysis to investigate how genetic and early environmental risk factors alter the development of the gut microbiota in infants at risk of CD. Results: Toward this end, we selected 31 infants from a large-scale prospective birth cohort study of infants with a first-degree relative with CD. We then performed rigorous multivariate association, cross-sectional, and longitudinal analyses using metagenomic and metabolomic data collected at birth, 3 months and 6 months of age to explore the impact of genetic predisposition and environmental risk factors on the gut microbiota composition, function, and metabolome prior to the introduction of trigger (gluten). These analyses revealed several microbial species, functional pathways, and metabolites that are associated with each genetic and environmental risk factor or that are differentially abundant between environmentally exposed and non-exposed infants or between time points. Among our significant findings, we found that cesarean section delivery is associated with a decreased abundance of Bacteroides vulgatus and Bacteroides dorei and of folate biosynthesis pathway and with an increased abundance of hydroxyphenylacetic acid, alterations that are implicated in immune system dysfunction and inflammatory conditions. Additionally, longitudinal analysis revealed that, in infants not exposed to any environmental risk factor, the abundances of Bacteroides uniformis and of metabolite 3-3-hydroxyphenylproprionic acid increase over time, while those for lipoic acid and methane metabolism pathways decrease, patterns that are linked to beneficial immunomodulatory and anti-inflammatory effects. Conclusions: Overall, our study provides unprecedented insights into major taxonomic and functional shifts in the developing gut microbiota of infants at risk of CD linking genetic and environmental risk factors to detrimental immunomodulatory and inflammatory effects. [MediaObject not available: see fulltext.].

@article{
 title = {A New Whole Genome Culture-Independent Diagnostic Test (WG-CIDT) for Rapid Detection of Salmonella in Lettuce},
 type = {article},
 year = {2020},
 keywords = {Salmonella,bioinformatics,culture-independent,lettuce,metagenomics,whole genome},
 volume = {11},
 month = {4},
 publisher = {Frontiers Media S.A.},
 day = {17},
 id = {5df33bfe-f601-3568-97c8-9c26688a62d5},
 created = {2025-10-30T12:26:01.011Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.011Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The rapid detection of foodborne microbial pathogens contaminating fresh fruits and vegetables during the intervening period between harvest and consumption could revolutionize microbial quality assurance of food usually consumed raw and those with a limited shelf life. We have developed a sensitive, shotgun whole genome sequencing protocol capable of detecting as few as 1 colony forming unit (cfu) of Salmonella enterica serovar Typhimurium spiked on 25 g of lettuce. The Ion Torrent sequencing platform was used to generate reads of globally amplified DNA from microbes recovered from the surface of lettuce followed by bioinformatic analyses of the nucleotide sequences to detect the presence of Salmonella. The test is rapid and sensitive, and appropriate for testing perishable foods, and those consumed raw, for Salmonella contamination. The test has the potential to be universally applicable to any microbial contaminant on lettuce as long as a suitable bioinformatics pipeline is available and validated. A universal test is expected to pave the way for preventive and precision food safety and the re-shaping of the entire spectrum of food safety investigations from the current disease-limiting, reactive procedure to a proactive, disease prevention process.},
 bibtype = {article},
 author = {Ogunremi, Dele and Dupras, Andrée Ann and Naushad, Sohail and Gao, Ruimin and Duceppe, Marc Olivier and Omidi, Katayoun and Márquez, Imelda Galván and Huang, Hongsheng and Goodridge, Lawrence and Lévesque, Roger C. and Hasan, Nur A. and Dadlani, Manoj and Dixon, Brent and Magierowski, Sebastian and Masson, Luke},
 doi = {10.3389/FMICB.2020.00602},
 journal = {Frontiers in Microbiology}
}

The rapid detection of foodborne microbial pathogens contaminating fresh fruits and vegetables during the intervening period between harvest and consumption could revolutionize microbial quality assurance of food usually consumed raw and those with a limited shelf life. We have developed a sensitive, shotgun whole genome sequencing protocol capable of detecting as few as 1 colony forming unit (cfu) of Salmonella enterica serovar Typhimurium spiked on 25 g of lettuce. The Ion Torrent sequencing platform was used to generate reads of globally amplified DNA from microbes recovered from the surface of lettuce followed by bioinformatic analyses of the nucleotide sequences to detect the presence of Salmonella. The test is rapid and sensitive, and appropriate for testing perishable foods, and those consumed raw, for Salmonella contamination. The test has the potential to be universally applicable to any microbial contaminant on lettuce as long as a suitable bioinformatics pipeline is available and validated. A universal test is expected to pave the way for preventive and precision food safety and the re-shaping of the entire spectrum of food safety investigations from the current disease-limiting, reactive procedure to a proactive, disease prevention process.

@article{
 title = {Microbial resolution of whole genome shotgun and 16S amplicon metagenomic sequencing using publicly available NEON data},
 type = {article},
 year = {2020},
 volume = {15},
 month = {2},
 publisher = {Public Library of Science},
 day = {1},
 id = {5de3f654-5c23-3e88-9c7b-871a46f8e003},
 created = {2025-10-30T12:26:01.078Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.078Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Microorganisms are ubiquitous in the biosphere, playing a crucial role in both biogeochemistry of the planet and human health. However, identifying these microorganisms and defining their function are challenging. Widely used approaches in comparative metagenomics, 16S amplicon sequencing and whole genome shotgun sequencing (WGS), have provided access to DNA sequencing analysis to identify microorganisms and evaluate diversity and abundance in various environments. However, advances in parallel high-throughput DNA sequencing in the past decade have introduced major hurdles, namely standardization of methods, data storage, reproducible interoperability of results, and data sharing. The National Ecological Observatory Network (NEON), established by the National Science Foundation, enables all researchers to address queries on a regional to continental scale around a variety of environmental challenges and provide high-quality, integrated, and standardized data from field sites across the U.S. As the amount of metagenomic data continues to grow, standardized procedures that allow results across projects to be assessed and compared is becoming increasingly important in the field of metagenomics. We demonstrate the feasibility of using publicly available NEON soil metagenomic sequencing datasets in combination with open access Metagenomics Rapid Annotation using the Subsystem Technology (MG-RAST) server to illustrate advantages of WGS compared to 16S amplicon sequencing. Four WGS and four 16S amplicon sequence datasets, from surface soil samples prepared by NEON investigators, were selected for comparison, using standardized protocols collected at the same locations in Colorado between April-July 2014. The dominant bacterial phyla detected across samples agreed between sequencing methodologies. However, WGS yielded greater microbial resolution, increased accuracy, and allowed identification of more genera of bacteria, archaea, viruses, and eukaryota, and putative functional genes that would have gone undetected using 16S amplicon sequencing. NEON open data will be useful for future studies characterizing and quantifying complex ecological processes associated with changing aquatic and terrestrial ecosystems.},
 bibtype = {article},
 author = {Brumfield, Kyle D. and Huq, Anwar and Colwell, Rita R. and Olds, James L. and Leddy, Menu B.},
 doi = {10.1371/JOURNAL.PONE.0228899},
 journal = {PLoS ONE},
 number = {2}
}

Microorganisms are ubiquitous in the biosphere, playing a crucial role in both biogeochemistry of the planet and human health. However, identifying these microorganisms and defining their function are challenging. Widely used approaches in comparative metagenomics, 16S amplicon sequencing and whole genome shotgun sequencing (WGS), have provided access to DNA sequencing analysis to identify microorganisms and evaluate diversity and abundance in various environments. However, advances in parallel high-throughput DNA sequencing in the past decade have introduced major hurdles, namely standardization of methods, data storage, reproducible interoperability of results, and data sharing. The National Ecological Observatory Network (NEON), established by the National Science Foundation, enables all researchers to address queries on a regional to continental scale around a variety of environmental challenges and provide high-quality, integrated, and standardized data from field sites across the U.S. As the amount of metagenomic data continues to grow, standardized procedures that allow results across projects to be assessed and compared is becoming increasingly important in the field of metagenomics. We demonstrate the feasibility of using publicly available NEON soil metagenomic sequencing datasets in combination with open access Metagenomics Rapid Annotation using the Subsystem Technology (MG-RAST) server to illustrate advantages of WGS compared to 16S amplicon sequencing. Four WGS and four 16S amplicon sequence datasets, from surface soil samples prepared by NEON investigators, were selected for comparison, using standardized protocols collected at the same locations in Colorado between April-July 2014. The dominant bacterial phyla detected across samples agreed between sequencing methodologies. However, WGS yielded greater microbial resolution, increased accuracy, and allowed identification of more genera of bacteria, archaea, viruses, and eukaryota, and putative functional genes that would have gone undetected using 16S amplicon sequencing. NEON open data will be useful for future studies characterizing and quantifying complex ecological processes associated with changing aquatic and terrestrial ecosystems.

@article{
 title = {SYN-007, an orally administered beta-lactamase enzyme, protects the gut microbiome from oral amoxicillin/clavulanate without adversely affecting antibiotic systemic absorption in dogs},
 type = {article},
 year = {2020},
 keywords = {Antibiotic,Beta-lactam,Beta-lactamase,Beta-lactamase inhibitor,Gut microbiome},
 volume = {8},
 month = {2},
 publisher = {MDPI AG},
 day = {1},
 id = {7f6696af-74d5-38ae-82e7-602c847d0a60},
 created = {2025-10-30T12:26:01.096Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:11.386Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Beta-lactamases, enzymes produced by bacteria to degrade beta-lactam antibiotics, have been harnessed as therapeutics to protect the gut microbiome from damage caused by antibiotics. Proof-of-concept of this approach using SYN-004 (ribaxamase), a beta-lactamase formulated for oral delivery with intravenous (IV) penicillins and cephalosporins, was demonstrated with animal models and in humans. Ribaxamase degraded ceftriaxone in the gastrointestinal tract, protected the gut microbiome, significantly reduced the incidence of Clostridioides difficile disease and attenuated emergence of antibiotic resistant organisms. SYN-007 is a delayed release formulation of ribaxamase intended for use with oral beta-lactams. In dogs treated with oral amoxicillin, SYN-007 diminished antibiotic-mediated microbiome disruption and reduced the emergence of antibiotic resistance without altering amoxicillin systemic absorption. Here, SYN-007 function in the presence of clavulanate, a beta-lactamase inhibitor, was investigated. Dogs received amoxicillin (40 mg/kg, orally (PO), three times a day (TID)) or the combined antibiotic/beta-lactamase inhibitor, amoxicillin/clavulanate (40 mg/kg amoxicillin, 5.7 mg/kg clavulanate, PO, TID) +/- SYN-007 (10 mg, PO, TID) for five days. Serum amoxicillin levels were not significantly different +/- SYN-007 compared to amoxicillin alone or amoxicillin/clavulanate alone as controls for both first and last doses, indicating SYN-007 did not interfere with systemic absorption of the antibiotic. Whole genome shotgun metagenomics analyses of the fecal microbiomes demonstrated both amoxicillin and amoxicillin/clavulanate significantly reduced diversity and increased the frequency of antibiotic resistance genes. Microbiome damage appeared more severe with amoxicillin/clavulanate. In contrast, with SYN-007, microbiome diversity was not significantly altered, and frequency of antibiotic resistance genes did not increase. Importantly, SYN-007 functioned in the presence of clavulanate to protect the gut microbiome indicating that SYN-007 activity was not inhibited by clavulanate in the dog gastrointestinal tract. SYN-007 has the potential to expand microbiome protection to beta-lactam/beta-lactamase inhibitor combinations delivered orally or systemically.},
 bibtype = {article},
 author = {Connelly, Sheila and Fanelli, Brian and Hasan, Nur A. and Colwell, Rita R. and Kaleko, Michael},
 doi = {10.3390/MICROORGANISMS8020152},
 journal = {Microorganisms},
 number = {2}
}

Beta-lactamases, enzymes produced by bacteria to degrade beta-lactam antibiotics, have been harnessed as therapeutics to protect the gut microbiome from damage caused by antibiotics. Proof-of-concept of this approach using SYN-004 (ribaxamase), a beta-lactamase formulated for oral delivery with intravenous (IV) penicillins and cephalosporins, was demonstrated with animal models and in humans. Ribaxamase degraded ceftriaxone in the gastrointestinal tract, protected the gut microbiome, significantly reduced the incidence of Clostridioides difficile disease and attenuated emergence of antibiotic resistant organisms. SYN-007 is a delayed release formulation of ribaxamase intended for use with oral beta-lactams. In dogs treated with oral amoxicillin, SYN-007 diminished antibiotic-mediated microbiome disruption and reduced the emergence of antibiotic resistance without altering amoxicillin systemic absorption. Here, SYN-007 function in the presence of clavulanate, a beta-lactamase inhibitor, was investigated. Dogs received amoxicillin (40 mg/kg, orally (PO), three times a day (TID)) or the combined antibiotic/beta-lactamase inhibitor, amoxicillin/clavulanate (40 mg/kg amoxicillin, 5.7 mg/kg clavulanate, PO, TID) +/- SYN-007 (10 mg, PO, TID) for five days. Serum amoxicillin levels were not significantly different +/- SYN-007 compared to amoxicillin alone or amoxicillin/clavulanate alone as controls for both first and last doses, indicating SYN-007 did not interfere with systemic absorption of the antibiotic. Whole genome shotgun metagenomics analyses of the fecal microbiomes demonstrated both amoxicillin and amoxicillin/clavulanate significantly reduced diversity and increased the frequency of antibiotic resistance genes. Microbiome damage appeared more severe with amoxicillin/clavulanate. In contrast, with SYN-007, microbiome diversity was not significantly altered, and frequency of antibiotic resistance genes did not increase. Importantly, SYN-007 functioned in the presence of clavulanate to protect the gut microbiome indicating that SYN-007 activity was not inhibited by clavulanate in the dog gastrointestinal tract. SYN-007 has the potential to expand microbiome protection to beta-lactam/beta-lactamase inhibitor combinations delivered orally or systemically.

@article{
 title = {Temporal resistome and microbial community dynamics in an intensive aquaculture facility with prophylactic antimicrobial treatment},
 type = {article},
 year = {2020},
 keywords = {Antimicrobial resistance,Antimicrobials,Aquaculture,Metagenome,Microbiome,Resistome},
 pages = {1-17},
 volume = {8},
 month = {12},
 publisher = {MDPI AG},
 day = {1},
 id = {63424f37-c09b-3e01-a49c-e716fff5b362},
 created = {2025-10-30T12:26:02.073Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:10.614Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Excessive use of antimicrobials in aquaculture is concerning, given possible environmental ramifications and the potential contribution to the spread of antimicrobial resistance (AR). In this study, we explored seasonal abundance of antimicrobial resistance genes and bacterial community composition in the water column of an intensive aquaculture pond stocked with Silver Carp (Hypophthalmichthys molitrix) prophylactically treated with sulfamethoprim (25% sulfadiazine; 5% trimethoprim), relative to an adjacent unstocked reservoir. Bacterial community composition was monitored using high-throughput sequencing of 16S rRNA gene amplicons in eight sampling profiles to determine seasonal dynamics, representing principal stages in the fish fattening cycle. In tandem, qPCR was applied to assess relative abundance of selected antimicrobial resistance genes (sul1, sul2, dfrA1, tetA and blaTEM) and class-1 integrons (int1). Concomitantly, resistomes were extrapolated from shotgun metagenomes in representative profiles. Analyses revealed increased relative abundance of sulfonamide and tetracycline resistance genes in fishpond-03, relative to pre-stocking and reservoir levels, whereas no significant differences were observed for genes encoding resistance to antimicrobials that were not used in the fishpond-03. Seasons strongly dictated bacterial community composition, with high abundance of cyanobacteria in summer and increased relative abundance of Flavobacterium in the winter. Our results indicate that prophylactic use of sulfonamides in intensive aquaculture ponds facilitates resistance suggesting that prophylactic use of these antimicrobials in aquaculture should be restricted.},
 bibtype = {article},
 author = {Patil, Hemant J. and Gatica, Joao and Zolti, Avihai and Benet-Perelberg, Ayana and Naor, Alon and Dror, Barak and Ashhab, Ashraf Al and Marman, Sophi and Hasan, Nur A. and Colwell, Rita R. and Sher, Daniel and Minz, Dror and Cytryn, Eddie},
 doi = {10.3390/MICROORGANISMS8121984},
 journal = {Microorganisms},
 number = {12}
}

Excessive use of antimicrobials in aquaculture is concerning, given possible environmental ramifications and the potential contribution to the spread of antimicrobial resistance (AR). In this study, we explored seasonal abundance of antimicrobial resistance genes and bacterial community composition in the water column of an intensive aquaculture pond stocked with Silver Carp (Hypophthalmichthys molitrix) prophylactically treated with sulfamethoprim (25% sulfadiazine; 5% trimethoprim), relative to an adjacent unstocked reservoir. Bacterial community composition was monitored using high-throughput sequencing of 16S rRNA gene amplicons in eight sampling profiles to determine seasonal dynamics, representing principal stages in the fish fattening cycle. In tandem, qPCR was applied to assess relative abundance of selected antimicrobial resistance genes (sul1, sul2, dfrA1, tetA and blaTEM) and class-1 integrons (int1). Concomitantly, resistomes were extrapolated from shotgun metagenomes in representative profiles. Analyses revealed increased relative abundance of sulfonamide and tetracycline resistance genes in fishpond-03, relative to pre-stocking and reservoir levels, whereas no significant differences were observed for genes encoding resistance to antimicrobials that were not used in the fishpond-03. Seasons strongly dictated bacterial community composition, with high abundance of cyanobacteria in summer and increased relative abundance of Flavobacterium in the winter. Our results indicate that prophylactic use of sulfonamides in intensive aquaculture ponds facilitates resistance suggesting that prophylactic use of these antimicrobials in aquaculture should be restricted.

@article{
 title = {Feasibility and Comparison Study of Fecal Sample Collection Methods in Healthy Volunteers and Solid Organ Transplant Recipients Using 16S rRNA and Metagenomics Approaches},
 type = {article},
 year = {2020},
 keywords = {16S rRNA sequencing,fecal samples,metagenomics,microbiome,transplantation},
 pages = {425-440},
 volume = {18},
 month = {10},
 publisher = {Mary Ann Liebert Inc.},
 day = {1},
 id = {5bb7bb7f-6570-340d-89bf-8ba4bfdcf666},
 created = {2025-10-30T12:26:02.376Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:02.376Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The human microbiome encompasses a variety of microorganisms that change dynamically and are in close contact with the body. The microbiome influences health and homeostasis, as well as the immune system, and any significant change in this equilibrium (dysbiosis) triggers both acute and chronic health conditions. Microbiome research has surged, in part, due to advanced sequencing technologies enabling rapid, accurate, and cost-effective identification of the microbiome. A major prerequisite for stool sample collection to study the gut microbiome in longitudinal prospective studies requires standardized protocols that can be easily replicated. However, there are still significant bottlenecks to stool specimen collection that contribute to low patient retention rates in microbiome studies. These barriers are further exacerbated in solid organ transplant recipients where diarrhea is estimated to occur in up to half the patient population. We sought to test two relatively easy sample collection methods (fecal swab and wipes) and compare them to the more cumbersome "gold"standard collection method (scoop) using two different sequencing technologies (16S ribosomal RNA sequencing and shotgun metagenomics). Our comparison of the collection methods shows that both the swabs and the wipes are comparable to the scoop method in terms of bacterial abundance and diversity. The swabs, however, were closer in representation to the scoop and were easier to collect and process compared to the wipes. Potential contamination of the swab and the wipe samples by abundant skin commensals was low in our analysis. Comparison of the two sequencing technologies showed that they were complementary, and that 16S sequencing provided enough coverage to detect and differentiate between bacterial species identified in the collected samples. Our pilot study demonstrates that alternative collection methods for stool sampling are a viable option in clinical applications, such as organ transplant studies. The use of these methods may result in better patient retention recruitment rates in serial microbiome studies.},
 bibtype = {article},
 author = {Kurian, Sunil M. and Gordon, Skyler and Barrick, Bethany and Dadlani, Manoj N. and Fanelli, Brian and Cornell, Jenny B. and Head, Steven R. and Marsh, Christopher L. and Case, Jamie},
 doi = {10.1089/BIO.2020.0032},
 journal = {Biopreservation and Biobanking},
 number = {5}
}

The human microbiome encompasses a variety of microorganisms that change dynamically and are in close contact with the body. The microbiome influences health and homeostasis, as well as the immune system, and any significant change in this equilibrium (dysbiosis) triggers both acute and chronic health conditions. Microbiome research has surged, in part, due to advanced sequencing technologies enabling rapid, accurate, and cost-effective identification of the microbiome. A major prerequisite for stool sample collection to study the gut microbiome in longitudinal prospective studies requires standardized protocols that can be easily replicated. However, there are still significant bottlenecks to stool specimen collection that contribute to low patient retention rates in microbiome studies. These barriers are further exacerbated in solid organ transplant recipients where diarrhea is estimated to occur in up to half the patient population. We sought to test two relatively easy sample collection methods (fecal swab and wipes) and compare them to the more cumbersome "gold"standard collection method (scoop) using two different sequencing technologies (16S ribosomal RNA sequencing and shotgun metagenomics). Our comparison of the collection methods shows that both the swabs and the wipes are comparable to the scoop method in terms of bacterial abundance and diversity. The swabs, however, were closer in representation to the scoop and were easier to collect and process compared to the wipes. Potential contamination of the swab and the wipe samples by abundant skin commensals was low in our analysis. Comparison of the two sequencing technologies showed that they were complementary, and that 16S sequencing provided enough coverage to detect and differentiate between bacterial species identified in the collected samples. Our pilot study demonstrates that alternative collection methods for stool sampling are a viable option in clinical applications, such as organ transplant studies. The use of these methods may result in better patient retention recruitment rates in serial microbiome studies.

@article{
 title = {Assessing Population Diversity of Brettanomyces Yeast Species and Identification of Strains for Brewing Applications.},
 type = {article},
 year = {2020},
 keywords = {4-ethylguaiacol,Dekkera bruxellensis,beta-glucosidase,brewing fermentation,genomics,high-throughput screening,maltose assimilation,phenolic off-flavor},
 pages = {637},
 volume = {11},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/32373090,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC7177047},
 month = {4},
 publisher = {Frontiers Media S.A.},
 day = {9},
 id = {d83c0902-07db-3f04-8272-17e074fb39d1},
 created = {2025-10-30T12:28:33.445Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:38.246Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Brettanomyces yeasts have gained popularity in many sectors of the biotechnological industry, specifically in the field of beer production, but also in wine and ethanol production. Their unique properties enable Brettanomyces to outcompete conventional brewer's yeast in industrially relevant traits such as production of ethanol and pleasant flavors. Recent advances in next-generation sequencing (NGS) and high-throughput screening techniques have facilitated large population studies allowing the selection of appropriate yeast strains with improved traits. In order to get a better understanding of Brettanomyces species and its potential for beer production, we sequenced the whole genome of 84 strains, which we make available to the scientific community and carried out several in vitro assays for brewing-relevant properties. The collection includes isolates from different substrates and geographical origin. Additionally, we have included two of the oldest Carlsberg Research Laboratory isolates. In this study, we reveal the phylogenetic pattern of Brettanomyces species by comparing the predicted proteomes of each strain. Furthermore, we show that the Brettanomyces collection is well described using similarity in genomic organization, and that there is a direct correlation between genomic background and phenotypic characteristics. Particularly, genomic patterns affecting flavor production, maltose assimilation, beta-glucosidase activity, and phenolic off-flavor (POF) production are reported. This knowledge yields new insights into Brettanomyces population survival strategies, artificial selection pressure, and loss of carbon assimilation traits. On a species-specific level, we have identified for the first time a POF negative Brettanomyces anomalus strain, without the main spoilage character of Brettanomyces species. This strain (CRL-90) has lost DaPAD1, making it incapable of converting ferulic acid to 4-ethylguaiacol (4-EG) and 4-ethylphenol (4-EP). This loss of function makes CRL-90 a good candidate for the production of characteristic Brettanomyces flavors in beverages, without the contaminant increase in POF. Overall, this study displays the potential of exploring Brettanomyces yeast species biodiversity to find strains with relevant properties applicable to the brewing industry.},
 bibtype = {article},
 author = {Colomer, Marc Serra and Chailyan, Anna and Fennessy, Ross T and Olsson, Kim Friis and Johnsen, Lea and Solodovnikova, Natalia and Forster, Jochen},
 doi = {10.3389/fmicb.2020.00637},
 journal = {Frontiers in microbiology}
}

Brettanomyces yeasts have gained popularity in many sectors of the biotechnological industry, specifically in the field of beer production, but also in wine and ethanol production. Their unique properties enable Brettanomyces to outcompete conventional brewer's yeast in industrially relevant traits such as production of ethanol and pleasant flavors. Recent advances in next-generation sequencing (NGS) and high-throughput screening techniques have facilitated large population studies allowing the selection of appropriate yeast strains with improved traits. In order to get a better understanding of Brettanomyces species and its potential for beer production, we sequenced the whole genome of 84 strains, which we make available to the scientific community and carried out several in vitro assays for brewing-relevant properties. The collection includes isolates from different substrates and geographical origin. Additionally, we have included two of the oldest Carlsberg Research Laboratory isolates. In this study, we reveal the phylogenetic pattern of Brettanomyces species by comparing the predicted proteomes of each strain. Furthermore, we show that the Brettanomyces collection is well described using similarity in genomic organization, and that there is a direct correlation between genomic background and phenotypic characteristics. Particularly, genomic patterns affecting flavor production, maltose assimilation, beta-glucosidase activity, and phenolic off-flavor (POF) production are reported. This knowledge yields new insights into Brettanomyces population survival strategies, artificial selection pressure, and loss of carbon assimilation traits. On a species-specific level, we have identified for the first time a POF negative Brettanomyces anomalus strain, without the main spoilage character of Brettanomyces species. This strain (CRL-90) has lost DaPAD1, making it incapable of converting ferulic acid to 4-ethylguaiacol (4-EG) and 4-ethylphenol (4-EP). This loss of function makes CRL-90 a good candidate for the production of characteristic Brettanomyces flavors in beverages, without the contaminant increase in POF. Overall, this study displays the potential of exploring Brettanomyces yeast species biodiversity to find strains with relevant properties applicable to the brewing industry.

@article{
 title = {Cyclic GMP–AMP signalling protects bacteria against viral infection},
 type = {article},
 year = {2019},
 keywords = {polar},
 pages = {691-695},
 volume = {574},
 websites = {https://www.nature.com/articles/s41586-019-1605-5},
 month = {9},
 publisher = {Nature Publishing Group},
 day = {18},
 id = {e9a2c32d-0180-35ec-8ec0-9188777dec90},
 created = {2025-07-07T13:25:19.887Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:19.887Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The cyclic GMP–AMP synthase (cGAS)–STING pathway is a central component of the cell-autonomous innate immune system in animals1,2. The cGAS protein is a sensor of cytosolic viral DNA and, upon sensing DNA, it produces a cyclic GMP–AMP (cGAMP) signalling molecule that binds to the STING protein and activates the immune response3–5. The production of cGAMP has also been detected in bacteria6, and has been shown, in Vibrio cholerae, to activate a phospholipase that degrades the inner bacterial membrane7. However, the biological role of cGAMP signalling in bacteria remains unknown. Here we show that cGAMP signalling is part of an antiphage defence system that is common in bacteria. This system is composed of a four-gene operon that encodes the bacterial cGAS and the associated phospholipase, as well as two enzymes with the eukaryotic-like domains E1, E2 and JAB. We show that this operon confers resistance against a wide variety of phages. Phage infection triggers the production of cGAMP, which—in turn—activates the phospholipase, leading to a loss of membrane integrity and to cell death before completion of phage reproduction. Diverged versions of this system appear in more than 10% of prokaryotic genomes, and we show that variants with effectors other than phospholipase also protect against phage infection. Our results suggest that the eukaryotic cGAS–STING antiviral pathway has ancient evolutionary roots that stem from microbial defences against phages. cGAMP signalling in bacteria mediates anti-phage defence, as part of a genetic system suggested to be the ancient ancestor of the animal cGAS–STING innate immune pathway.},
 bibtype = {article},
 author = {Cohen, Daniel and Melamed, Sarah and Millman, Adi and Shulman, Gabriela and Oppenheimer-Shaanan, Yaara and Kacen, Assaf and Doron, Shany and Amitai, Gil and Sorek, Rotem},
 doi = {10.1038/s41586-019-1605-5},
 journal = {Nature 2019 574:7780},
 number = {7780}
}

The cyclic GMP–AMP synthase (cGAS)–STING pathway is a central component of the cell-autonomous innate immune system in animals1,2. The cGAS protein is a sensor of cytosolic viral DNA and, upon sensing DNA, it produces a cyclic GMP–AMP (cGAMP) signalling molecule that binds to the STING protein and activates the immune response3–5. The production of cGAMP has also been detected in bacteria6, and has been shown, in Vibrio cholerae, to activate a phospholipase that degrades the inner bacterial membrane7. However, the biological role of cGAMP signalling in bacteria remains unknown. Here we show that cGAMP signalling is part of an antiphage defence system that is common in bacteria. This system is composed of a four-gene operon that encodes the bacterial cGAS and the associated phospholipase, as well as two enzymes with the eukaryotic-like domains E1, E2 and JAB. We show that this operon confers resistance against a wide variety of phages. Phage infection triggers the production of cGAMP, which—in turn—activates the phospholipase, leading to a loss of membrane integrity and to cell death before completion of phage reproduction. Diverged versions of this system appear in more than 10% of prokaryotic genomes, and we show that variants with effectors other than phospholipase also protect against phage infection. Our results suggest that the eukaryotic cGAS–STING antiviral pathway has ancient evolutionary roots that stem from microbial defences against phages. cGAMP signalling in bacteria mediates anti-phage defence, as part of a genetic system suggested to be the ancient ancestor of the animal cGAS–STING innate immune pathway.

@article{
 title = {Development of advanced analytical methodologies based on gas chromatography coupled to mass spectometry for the determination of pops and vocs in the food and environmental field},
 type = {article},
 year = {2019},
 keywords = {543,Ciències naturals,Gas Chromatography,Mass Spectrometry,Metabolomics,Pollutants,Purge and Trap,Volatiles,físiques i matemàtiques,químiques},
 websites = {https://www.tdx.cat/handle/10803/668939},
 month = {12},
 publisher = {Universitat Jaume I},
 day = {18},
 city = {Castelló},
 institution = {Universitat Jaume I},
 department = {Química Física i Analítica},
 id = {15354d97-669a-3caf-ade5-55b843b2441b},
 created = {2025-07-07T13:25:20.219Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:06.775Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Programa de Doctorat en Ciències},
 bibtype = {article},
 author = {Sales Martínez, Carlos},
 doi = {10.6035/14104.2019.177055},
 journal = {TDX (Tesis Doctorals en Xarxa)}
}

Programa de Doctorat en Ciències

@article{
 title = {High Levels of Prebiotic Resistant Starch in Diet Modulate Gene Expression and Metabolomic Profile in Pancreatic Cancer Xenograft Mice},
 type = {article},
 year = {2019},
 keywords = {Animals,Annacandida Villani,Concetta Panebianco,Diet / adverse effects*,Gene Expression / physiology*,Heterografts,MEDLINE,Metabolomics,Mice,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Nutrigenomics,PMC6521226,Pancreatic Neoplasms / etiology,Pancreatic Neoplasms / metabolism*,Pancreatic Neoplasms / microbiology,Prebiotics,PubMed Abstract,Starch / adverse effects*,Valerio Pazienza,doi:10.3390/nu11040709,pmid:30934731},
 volume = {11},
 websites = {https://pubmed.ncbi.nlm.nih.gov/30934731/},
 month = {4},
 publisher = {Nutrients},
 day = {1},
 id = {86fd9c93-6684-3416-ae37-20e5ca112779},
 created = {2025-07-07T13:25:20.574Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:07.271Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Cancer initiation and protection mainly derives from a systemic metabolic environment regulated by dietary patterns. Less is known about the impact of nutritional interventions in people with a diagnosis of cancer. The aim of our study was to investigate the effect of a diet rich in resistant starch (RS) on cell pathways modulation and metabolomic phenotype in pancreatic cancer xenograft mice. RNA-Seq experiments on tumor tissue showed that 25 genes resulted in dysregulated pancreatic cancer in mice fed with an RS diet, as compared to those fed with control diet. Moreover, in these two different mice groups, six serum metabolites were deregulated as detected by LC–MS analysis. A bioinformatic prediction analysis showed the involvement of the differentially expressed genes on insulin receptor signaling, circadian rhythm signaling, and cancer drug resistance among the three top canonical pathways, whilst cell death and survival, gene expression, and neurological disease were among the three top disease and biological functions. These findings shed light on the genomic and metabolic phenotype, contributing to the knowledge of the mechanisms through which RS may act as a potential supportive approach for enhancing the efficacy of existing cancer treatments.},
 bibtype = {article},
 author = {Panebianco, Concetta and Villani, Annacandida and Pazienza, Valerio},
 doi = {10.3390/NU11040709},
 journal = {Nutrients},
 number = {4}
}

Cancer initiation and protection mainly derives from a systemic metabolic environment regulated by dietary patterns. Less is known about the impact of nutritional interventions in people with a diagnosis of cancer. The aim of our study was to investigate the effect of a diet rich in resistant starch (RS) on cell pathways modulation and metabolomic phenotype in pancreatic cancer xenograft mice. RNA-Seq experiments on tumor tissue showed that 25 genes resulted in dysregulated pancreatic cancer in mice fed with an RS diet, as compared to those fed with control diet. Moreover, in these two different mice groups, six serum metabolites were deregulated as detected by LC–MS analysis. A bioinformatic prediction analysis showed the involvement of the differentially expressed genes on insulin receptor signaling, circadian rhythm signaling, and cancer drug resistance among the three top canonical pathways, whilst cell death and survival, gene expression, and neurological disease were among the three top disease and biological functions. These findings shed light on the genomic and metabolic phenotype, contributing to the knowledge of the mechanisms through which RS may act as a potential supportive approach for enhancing the efficacy of existing cancer treatments.

@article{
 title = {In vitro Characterization of Gut Microbiota-Derived Bacterial Strains With Neuroprotective Properties},
 type = {article},
 year = {2019},
 keywords = {gut microbiota-derived bacterial strains,gut-brain axis,microbiome,neurodegenerative diseases,neuroinflammation,neuroprotection,oxidative stress,short-chain fatty acids},
 pages = {463586},
 volume = {13},
 month = {9},
 publisher = {Frontiers Media S.A.},
 day = {20},
 id = {8ccf8162-4dd2-38c6-8611-f434b0050a53},
 created = {2025-07-07T13:25:20.920Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:07.610Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Neurodegenerative diseases are disabling, incurable, and progressive conditions characterized by neuronal loss and decreased cognitive function. Changes in gut microbiome composition have been linked to a number of neurodegenerative diseases, indicating a role for the gut-brain axis. Here, we show how specific gut-derived bacterial strains can modulate neuroinflammatory and neurodegenerative processes in vitro through the production of specific metabolites and discuss the potential therapeutic implications for neurodegenerative disorders. A panel of fifty gut bacterial strains was screened for their ability to reduce pro-inflammatory IL-6 secretion in U373 glioblastoma astrocytoma cells. Parabacteroides distasonis MRx0005 and Megasphaera massiliensis MRx0029 had the strongest capacity to reduce IL-6 secretion in vitro. Oxidative stress plays a crucial role in neuroinflammation and neurodegeneration, and both bacterial strains displayed intrinsic antioxidant capacity. While MRx0005 showed a general antioxidant activity on different brain cell lines, MRx0029 only protected differentiated SH-SY5Y neuroblastoma cells from chemically induced oxidative stress. MRx0029 also induced a mature phenotype in undifferentiated neuroblastoma cells through upregulation of microtubule-associated protein 2. Interestingly, short-chain fatty acid analysis revealed that MRx0005 mainly produced C1-C3 fatty acids, while MRx0029 produced C4-C6 fatty acids, specifically butyric, valeric and hexanoic acid. None of the short-chain fatty acids tested protected neuroblastoma cells from chemically induced oxidative stress. However, butyrate was able to reduce neuroinflammation in vitro, and the combination of butyrate and valerate induced neuronal maturation, albeit not to the same degree as the complex cell-free supernatant of MRx0029. This observation was confirmed by solvent extraction of cell-free supernatants, where only MRx0029 methanolic fractions containing butyrate and valerate showed an anti-inflammatory activity in U373 cells and retained the ability to differentiate neuroblastoma cells. In summary, our results suggest that the pleiotropic nature of live biotherapeutics, as opposed to isolated metabolites, could be a promising novel drug class in drug discovery for neurodegenerative disorders.},
 bibtype = {article},
 author = {Ahmed, Suaad and Busetti, Alessandro and Fotiadou, Parthena and Vincy Jose, Nisha and Reid, Sarah and Georgieva, Marieta and Brown, Samantha and Dunbar, Hayley and Beurket-Ascencio, Gloria and Delday, Margaret I. and Ettorre, Anna and Mulder, Imke E.},
 doi = {10.3389/FNCEL.2019.00402/BIBTEX},
 journal = {Frontiers in Cellular Neuroscience}
}

Neurodegenerative diseases are disabling, incurable, and progressive conditions characterized by neuronal loss and decreased cognitive function. Changes in gut microbiome composition have been linked to a number of neurodegenerative diseases, indicating a role for the gut-brain axis. Here, we show how specific gut-derived bacterial strains can modulate neuroinflammatory and neurodegenerative processes in vitro through the production of specific metabolites and discuss the potential therapeutic implications for neurodegenerative disorders. A panel of fifty gut bacterial strains was screened for their ability to reduce pro-inflammatory IL-6 secretion in U373 glioblastoma astrocytoma cells. Parabacteroides distasonis MRx0005 and Megasphaera massiliensis MRx0029 had the strongest capacity to reduce IL-6 secretion in vitro. Oxidative stress plays a crucial role in neuroinflammation and neurodegeneration, and both bacterial strains displayed intrinsic antioxidant capacity. While MRx0005 showed a general antioxidant activity on different brain cell lines, MRx0029 only protected differentiated SH-SY5Y neuroblastoma cells from chemically induced oxidative stress. MRx0029 also induced a mature phenotype in undifferentiated neuroblastoma cells through upregulation of microtubule-associated protein 2. Interestingly, short-chain fatty acid analysis revealed that MRx0005 mainly produced C1-C3 fatty acids, while MRx0029 produced C4-C6 fatty acids, specifically butyric, valeric and hexanoic acid. None of the short-chain fatty acids tested protected neuroblastoma cells from chemically induced oxidative stress. However, butyrate was able to reduce neuroinflammation in vitro, and the combination of butyrate and valerate induced neuronal maturation, albeit not to the same degree as the complex cell-free supernatant of MRx0029. This observation was confirmed by solvent extraction of cell-free supernatants, where only MRx0029 methanolic fractions containing butyrate and valerate showed an anti-inflammatory activity in U373 cells and retained the ability to differentiate neuroblastoma cells. In summary, our results suggest that the pleiotropic nature of live biotherapeutics, as opposed to isolated metabolites, could be a promising novel drug class in drug discovery for neurodegenerative disorders.

@article{
 title = {Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR},
 type = {article},
 year = {2019},
 keywords = {IL-23,UPR,dendritic cells,fatty acids,glycolysis,hexokinase,innate immunity,metabolic reprogramming,mtROS,psoriasis},
 pages = {1201-1216.e19},
 volume = {177},
 websites = {http://www.cell.com/article/S0092867419302806/fulltext,http://www.cell.com/article/S0092867419302806/abstract,https://www.cell.com/cell/abstract/S0092-8674(19)30280-6},
 month = {5},
 publisher = {Cell Press},
 day = {16},
 id = {43a1292a-2e1d-39dd-ad2e-1cf87a6f3bce},
 created = {2025-07-07T13:25:21.293Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:08.024Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Innate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-like receptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatory signals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect the immune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DCs) are exacerbated by a high-fatty-acid (FA) metabolic environment. FAs suppress the TLR-induced hexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changes enhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded protein response (UPR), leading to a distinct transcriptomic signature with IL-23 as hallmark. Interestingly, chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response. Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23 expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innate immunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR. A high-fat diet induces the metabolic rewiring of TLR-activated dendritic cells and exacerbates IL-23-mediated psoriatic skin inflammation.},
 bibtype = {article},
 author = {Mogilenko, Denis A. and Haas, Joel T. and L'homme, Laurent and Fleury, Sébastien and Quemener, Sandrine and Levavasseur, Matthieu and Becquart, Coralie and Wartelle, Julien and Bogomolova, Alexandra and Pineau, Laurent and Molendi-Coste, Olivier and Lancel, Steve and Dehondt, Hélène and Gheeraert, Celine and Melchior, Aurelie and Dewas, Cédric and Nikitin, Artemii and Pic, Samuel and Rabhi, Nabil and Annicotte, Jean Sébastien and Oyadomari, Seiichi and Velasco-Hernandez, Talia and Cammenga, Jörg and Foretz, Marc and Viollet, Benoit and Vukovic, Milica and Villacreces, Arnaud and Kranc, Kamil and Carmeliet, Peter and Marot, Guillemette and Boulter, Alexis and Tavernier, Simon and Berod, Luciana and Longhi, Maria P. and Paget, Christophe and Janssens, Sophie and Staumont-Sallé, Delphine and Aksoy, Ezra and Staels, Bart and Dombrowicz, David},
 doi = {10.1016/j.cell.2019.03.018},
 journal = {Cell},
 number = {5}
}

Innate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-like receptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatory signals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect the immune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DCs) are exacerbated by a high-fatty-acid (FA) metabolic environment. FAs suppress the TLR-induced hexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changes enhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded protein response (UPR), leading to a distinct transcriptomic signature with IL-23 as hallmark. Interestingly, chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response. Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23 expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innate immunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR. A high-fat diet induces the metabolic rewiring of TLR-activated dendritic cells and exacerbates IL-23-mediated psoriatic skin inflammation.

@article{
 title = {Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells},
 type = {article},
 year = {2019},
 keywords = {Bone,Fat metabolism},
 pages = {1-14},
 volume = {7},
 websites = {https://www.nature.com/articles/s41413-019-0076-5},
 month = {11},
 publisher = {Nature Publishing Group},
 day = {14},
 id = {ae03ed37-082f-3bcc-9fc0-37d3657c1bcc},
 created = {2025-07-07T13:25:21.655Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:08.339Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Enhanced bone marrow adipogenesis and impaired osteoblastogenesis have been observed in obesity, suggesting that the metabolic microenvironment regulates bone marrow adipocyte and osteoblast progenitor differentiation fate. To determine the molecular mechanisms, we studied two immortalized murine cell lines of adipocyte or osteoblast progenitors (BMSCsadipo and BMSCsosteo, respectively) under basal and adipogenic culture conditions. At baseline, BMSCsadipo, and BMSCsosteo exhibit a distinct metabolic program evidenced by the presence of specific global gene expression, cellular bioenergetics, and metabolomic signatures that are dependent on insulin signaling and glycolysis in BMSCsosteo versus oxidative phosphorylation in BMSCsadipo. To test the flexibility of the metabolic program, we treated BMSCsadipo with parathyroid hormone, S961 (an inhibitor of insulin signaling) and oligomycin (an inhibitor of oxidative phosphorylation). The treatment induced significant changes in cellular bioenergetics that were associated with decreased adipocytic differentiation. Similarly, 12 weeks of a high-fat diet in mice led to the expansion of adipocyte progenitors, enhanced adipocyte differentiation and insulin signaling in cultured BMSCs. Our data demonstrate that BMSC progenitors possess a distinct metabolic program and are poised to respond to exogenous metabolic cues that regulate their differentiation fate.},
 bibtype = {article},
 author = {Tencerova, Michaela and Rendina-Ruedy, Elizabeth and Neess, Ditte and Færgeman, Nils and Figeac, Florence and Ali, Dalia and Danielsen, Morten and Haakonsson, Anders and Rosen, Clifford J. and Kassem, Moustapha},
 doi = {10.1038/s41413-019-0076-5},
 journal = {Bone Research 2019 7:1},
 number = {1}
}

Enhanced bone marrow adipogenesis and impaired osteoblastogenesis have been observed in obesity, suggesting that the metabolic microenvironment regulates bone marrow adipocyte and osteoblast progenitor differentiation fate. To determine the molecular mechanisms, we studied two immortalized murine cell lines of adipocyte or osteoblast progenitors (BMSCsadipo and BMSCsosteo, respectively) under basal and adipogenic culture conditions. At baseline, BMSCsadipo, and BMSCsosteo exhibit a distinct metabolic program evidenced by the presence of specific global gene expression, cellular bioenergetics, and metabolomic signatures that are dependent on insulin signaling and glycolysis in BMSCsosteo versus oxidative phosphorylation in BMSCsadipo. To test the flexibility of the metabolic program, we treated BMSCsadipo with parathyroid hormone, S961 (an inhibitor of insulin signaling) and oligomycin (an inhibitor of oxidative phosphorylation). The treatment induced significant changes in cellular bioenergetics that were associated with decreased adipocytic differentiation. Similarly, 12 weeks of a high-fat diet in mice led to the expansion of adipocyte progenitors, enhanced adipocyte differentiation and insulin signaling in cultured BMSCs. Our data demonstrate that BMSC progenitors possess a distinct metabolic program and are poised to respond to exogenous metabolic cues that regulate their differentiation fate.

@article{
 title = {Metabolomics Analyses in High-Low Feed Efficient Dairy Cows Reveal Novel Biochemical Mechanisms and Predictive Biomarkers},
 type = {article},
 year = {2019},
 keywords = {Dairy cattle,Gene-metabolite network,Metabolomics,Residual feed intake},
 volume = {9},
 websites = {/pmc/articles/PMC6680417/,/pmc/articles/PMC6680417/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680417/},
 month = {7},
 publisher = {Multidisciplinary Digital Publishing Institute  (MDPI)},
 day = {1},
 id = {4a577d49-ed14-3b6b-a18d-dc4ec7cf1d88},
 created = {2025-07-07T13:25:22.043Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:08.758Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Residual feed intake (RFI) is designed to estimate net efficiency of feed use, so low RFI animals are considered for selection to reduce feeding costs. However, metabolic profiling of cows and availability of predictive metabolic biomarkers for RFI are scarce. Therefore, this study aims to generate a better understanding of metabolic mechanisms behind low and high RFI in Jerseys and Holsteins and identify potential predictive metabolic biomarkers. Each metabolite was analyzed to reveal their associations with two RFIs in two breeds by a linear regression model. An integrative analysis of metabolomics and transcriptomics was performed to explore interactions between functionally related metabolites and genes in the created metabolite networks. We found that three main clusters were detected in the heat map and all identified fatty acids (palmitoleic, hexadecanoic, octadecanoic, heptadecanoic, and tetradecanoic acid) were grouped in a cluster. The lower cluster were all from fatty acids, including palmitoleic acid, hexadecanoic acid, octadecanoic acid, heptadecanoic acid, and tetradecanoic acid. The first component of the partial least squares-discriminant analysis (PLS-DA) explained a majority (61.5%) of variations of all metabolites. A good division between two breeds was also observed. Significant differences between low and high RFIs existed in the fatty acid group (P < 0.001). Statistical results revealed clearly significant differences between breeds; however, the association of individual metabolites (leucine, ornithine, pentadecanoic acid, and valine) with the RFI status was only marginally significant or not significant due to a lower sample size. The integrated gene-metabolite pathway analysis showed that pathway impact values were higher than those of a single metabolic pathway. Both types of pathway analyses revealed three important pathways, which were aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and the citrate cycle (TCA cycle). Finally, one gene (2-hydroxyacyl-CoA lyase 1 (+HACL1)) associated with two metabolites (-α-ketoglutarate and succinic acid) were identified in the gene-metabolite interaction network. This study provided novel metabolic pathways and integrated metabolic-gene expression networks in high and low RFI Holstein and Jersey cattle, thereby providing a better understanding of novel biochemical mechanisms underlying variation in feed efficiency.},
 bibtype = {article},
 author = {Wang, Xiao and Kadarmideen, Haja N.},
 doi = {10.3390/METABO9070151},
 journal = {Metabolites},
 number = {7}
}

Residual feed intake (RFI) is designed to estimate net efficiency of feed use, so low RFI animals are considered for selection to reduce feeding costs. However, metabolic profiling of cows and availability of predictive metabolic biomarkers for RFI are scarce. Therefore, this study aims to generate a better understanding of metabolic mechanisms behind low and high RFI in Jerseys and Holsteins and identify potential predictive metabolic biomarkers. Each metabolite was analyzed to reveal their associations with two RFIs in two breeds by a linear regression model. An integrative analysis of metabolomics and transcriptomics was performed to explore interactions between functionally related metabolites and genes in the created metabolite networks. We found that three main clusters were detected in the heat map and all identified fatty acids (palmitoleic, hexadecanoic, octadecanoic, heptadecanoic, and tetradecanoic acid) were grouped in a cluster. The lower cluster were all from fatty acids, including palmitoleic acid, hexadecanoic acid, octadecanoic acid, heptadecanoic acid, and tetradecanoic acid. The first component of the partial least squares-discriminant analysis (PLS-DA) explained a majority (61.5%) of variations of all metabolites. A good division between two breeds was also observed. Significant differences between low and high RFIs existed in the fatty acid group (P < 0.001). Statistical results revealed clearly significant differences between breeds; however, the association of individual metabolites (leucine, ornithine, pentadecanoic acid, and valine) with the RFI status was only marginally significant or not significant due to a lower sample size. The integrated gene-metabolite pathway analysis showed that pathway impact values were higher than those of a single metabolic pathway. Both types of pathway analyses revealed three important pathways, which were aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and the citrate cycle (TCA cycle). Finally, one gene (2-hydroxyacyl-CoA lyase 1 (+HACL1)) associated with two metabolites (-α-ketoglutarate and succinic acid) were identified in the gene-metabolite interaction network. This study provided novel metabolic pathways and integrated metabolic-gene expression networks in high and low RFI Holstein and Jersey cattle, thereby providing a better understanding of novel biochemical mechanisms underlying variation in feed efficiency.

@article{
 title = {Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome},
 type = {article},
 year = {2019},
 keywords = {Molecular biology,Neuroscience},
 pages = {2567-2583},
 volume = {25},
 websites = {https://www.nature.com/articles/s41380-019-0425-1},
 month = {5},
 publisher = {Nature Publishing Group},
 day = {16},
 id = {d9fab3a7-a18a-3133-9ef8-3769fb9cfa4c},
 created = {2025-07-07T13:25:22.371Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:22.371Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Male middle age is a transitional period where many physiological and psychological changes occur leading to cognitive and behavioural alterations, and a deterioration of brain function. However, the mechanisms underpinning such changes are unclear. The gut microbiome has been implicated as a key mediator in the communication between the gut and the brain, and in the regulation of brain homeostasis, including brain immune cell function. Thus, we tested whether targeting the gut microbiome by prebiotic supplementation may alter microglia activation and brain function in ageing. Male young adult (8 weeks) and middle-aged (10 months) C57BL/6 mice received diet enriched with a prebiotic (10% oligofructose-enriched inulin) or control chow for 14 weeks. Prebiotic supplementation differentially altered the gut microbiota profile in young and middle-aged mice with changes correlating with faecal metabolites. Functionally, this translated into a reversal of stress-induced immune priming in middle-aged mice. In addition, a reduction in ageing-induced infiltration of Ly-6Chi monocytes into the brain coupled with a reversal in ageing-related increases in a subset of activated microglia (Ly-6C+) was observed. Taken together, these data highlight a potential pathway by which targeting the gut microbiome with prebiotics can modulate the peripheral immune response and alter neuroinflammation in middle age. Our data highlight a novel strategy for the amelioration of age-related neuroinflammatory pathologies and brain function.},
 bibtype = {article},
 author = {Boehme, Marcus and van de Wouw, Marcel and Bastiaanssen, Thomaz F.S. and Olavarría-Ramírez, Loreto and Lyons, Katriona and Fouhy, Fiona and Golubeva, Anna V. and Moloney, Gerard M. and Minuto, Chiara and Sandhu, Kiran V. and Scott, Karen A. and Clarke, Gerard and Stanton, Catherine and Dinan, Timothy G. and Schellekens, Harriët and Cryan, John F.},
 doi = {10.1038/s41380-019-0425-1},
 journal = {Molecular Psychiatry 2019 25:10},
 number = {10}
}

Male middle age is a transitional period where many physiological and psychological changes occur leading to cognitive and behavioural alterations, and a deterioration of brain function. However, the mechanisms underpinning such changes are unclear. The gut microbiome has been implicated as a key mediator in the communication between the gut and the brain, and in the regulation of brain homeostasis, including brain immune cell function. Thus, we tested whether targeting the gut microbiome by prebiotic supplementation may alter microglia activation and brain function in ageing. Male young adult (8 weeks) and middle-aged (10 months) C57BL/6 mice received diet enriched with a prebiotic (10% oligofructose-enriched inulin) or control chow for 14 weeks. Prebiotic supplementation differentially altered the gut microbiota profile in young and middle-aged mice with changes correlating with faecal metabolites. Functionally, this translated into a reversal of stress-induced immune priming in middle-aged mice. In addition, a reduction in ageing-induced infiltration of Ly-6Chi monocytes into the brain coupled with a reversal in ageing-related increases in a subset of activated microglia (Ly-6C+) was observed. Taken together, these data highlight a potential pathway by which targeting the gut microbiome with prebiotics can modulate the peripheral immune response and alter neuroinflammation in middle age. Our data highlight a novel strategy for the amelioration of age-related neuroinflammatory pathologies and brain function.

@article{
 title = {Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice},
 type = {article},
 year = {2019},
 keywords = {Diet-induced obesity,Host-microbe interactions,Human defensins,Insulin resistance,NAFLD},
 pages = {E42-E52},
 volume = {317},
 id = {fd085c6f-35a2-338f-a448-990ccdcea5b2},
 created = {2025-07-07T13:25:22.708Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:09.167Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Overnutrition is the principal cause of insulin resis-tance (IR) and dyslipidemia, which drive nonalcoholic fatty liver disease (NAFLD). Overnutrition is further linked to disrupted bowel function, microbiota alterations, and change of function in gut-lining cell populations, including Paneth cells of the small intestine. Paneth cells regulate microbial diversity through expression of antimicrobial peptides, particularly human α-defensin-5 (HD-5), and have shown repressed secretory capacity in human obesity. Mice were fed a 60% high-fat diet for 13 wk and subsequently treated with physiologically relevant amounts of HD-5 (0.001%) or vehicle for 10 wk. The glucoregulatory capacity was determined by glucose tolerance tests and measurements of corresponding insulin concentrations both before and during intervention. Gut microbiome composition was examined by 16S rRNA gene amplicon sequencing. HD-5-treated mice exhibited improved glucoregulatory capacity along with an ameliorated plasma and liver lipid profile. This was accompanied by specific decrease in jejunal inflammation and gut microbiota alterations including increased Bifidobacterium abundances, which correlated inversely with metabolic dysfunctions. This study provides proof of concept for the use of human defensins to improve host metabolism by mitigating the triad cluster of dyslipidemia, IR, and NAFLD.},
 bibtype = {article},
 author = {Larsen, Ida Søgaard and Fritzen, Andreas Mæchel and Carl, Christian Strini and Agerholm, Marianne and Damgaard, Mads Thue Fejerskov and Holm, Jacob Bak and Marette, André and Nordkild, Peter and Kiens, Bente and Kristiansen, Karsten and Wehkamp, Jan and Jensen, Benjamin Anderschou Holbech},
 doi = {10.1152/ajpendo.00019.2019},
 journal = {American Journal of Physiology - Endocrinology and Metabolism},
 number = {1}
}

Overnutrition is the principal cause of insulin resis-tance (IR) and dyslipidemia, which drive nonalcoholic fatty liver disease (NAFLD). Overnutrition is further linked to disrupted bowel function, microbiota alterations, and change of function in gut-lining cell populations, including Paneth cells of the small intestine. Paneth cells regulate microbial diversity through expression of antimicrobial peptides, particularly human α-defensin-5 (HD-5), and have shown repressed secretory capacity in human obesity. Mice were fed a 60% high-fat diet for 13 wk and subsequently treated with physiologically relevant amounts of HD-5 (0.001%) or vehicle for 10 wk. The glucoregulatory capacity was determined by glucose tolerance tests and measurements of corresponding insulin concentrations both before and during intervention. Gut microbiome composition was examined by 16S rRNA gene amplicon sequencing. HD-5-treated mice exhibited improved glucoregulatory capacity along with an ameliorated plasma and liver lipid profile. This was accompanied by specific decrease in jejunal inflammation and gut microbiota alterations including increased Bifidobacterium abundances, which correlated inversely with metabolic dysfunctions. This study provides proof of concept for the use of human defensins to improve host metabolism by mitigating the triad cluster of dyslipidemia, IR, and NAFLD.

@article{
 title = {Bifidobacterium breve Bif195 Protects Against Small-Intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers},
 type = {article},
 year = {2019},
 keywords = {Aspirin,Bacteria,Bleeding,Microbiota},
 pages = {637-646.e4},
 volume = {157},
 websites = {https://doi.org/10.1053/j.gastro.2019.05.008},
 publisher = {The American Gastroenterological Association},
 id = {b27f9e89-5cd1-3027-95f3-43276acdde71},
 created = {2025-07-07T13:25:23.033Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:09.554Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Mortensen2019},
 private_publication = {false},
 abstract = {Background & Aims: Enteropathy and small-intestinal ulcers are common adverse effects of nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA). Safe, cytoprotective strategies are needed to reduce this risk. Specific bifidobacteria might have cytoprotective activities, but little is known about these effects in humans. We used serial video capsule endoscopy (VCE) to assess the efficacy of a specific Bifidobacterium strain in healthy volunteers exposed to ASA. Methods: We performed a single-site, double-blind, parallel-group, proof-of-concept analysis of 75 heathy volunteers given ASA (300 mg) daily for 6 weeks, from July 31 through October 24, 2017. The participants were randomly assigned (1:1) to groups given oral capsules of Bifidobacterium breve (Bif195) (≥5 × 1010 colony-forming units) or placebo daily for 8 weeks. Small-intestinal damage was analyzed by serial VCE at 6 visits. The area under the curve (AUC) for intestinal damage (Lewis score) and the AUC value for ulcers were the primary and first-ranked secondary end points of the trial, respectively. Results: Efficacy data were obtained from 35 participants given Bif195 and 31 given placebo. The AUC for Lewis score was significantly lower in the Bif195 group (3040 ± 1340 arbitrary units) than the placebo group (4351 ± 3195) (P =.0376). The AUC for ulcer number was significantly lower in the Bif195 group (50.4 ± 53.1 arbitrary units) than in the placebo group (75.2 ± 85.3 arbitrary units) (P =.0258). Twelve adverse events were reported from the Bif195 group and 20 from the placebo group. None of the events was determined to be related to Bif195 intake. Conclusions: In a randomized, double-blind trial of healthy volunteers, we found oral Bif195 to safely reduce the risk of small-intestinal enteropathy caused by ASA. ClinicalTrials.gov no: NCT03228589.},
 bibtype = {article},
 author = {Mortensen, Brynjulf and Murphy, Clodagh and O'Grady, John and Lucey, Mary and Elsafi, Gafer and Barry, Lillian and Westphal, Vibeke and Wellejus, Anja and Lukjancenko, Oksana and Eklund, Aron C. and Nielsen, Henrik Bjørn and Baker, Adam and Damholt, Anders and van Hylckama Vlieg, Johan E.T. and Shanahan, Fergus and Buckley, Martin},
 doi = {10.1053/j.gastro.2019.05.008},
 journal = {Gastroenterology},
 number = {3}
}

Background & Aims: Enteropathy and small-intestinal ulcers are common adverse effects of nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA). Safe, cytoprotective strategies are needed to reduce this risk. Specific bifidobacteria might have cytoprotective activities, but little is known about these effects in humans. We used serial video capsule endoscopy (VCE) to assess the efficacy of a specific Bifidobacterium strain in healthy volunteers exposed to ASA. Methods: We performed a single-site, double-blind, parallel-group, proof-of-concept analysis of 75 heathy volunteers given ASA (300 mg) daily for 6 weeks, from July 31 through October 24, 2017. The participants were randomly assigned (1:1) to groups given oral capsules of Bifidobacterium breve (Bif195) (≥5 × 1010 colony-forming units) or placebo daily for 8 weeks. Small-intestinal damage was analyzed by serial VCE at 6 visits. The area under the curve (AUC) for intestinal damage (Lewis score) and the AUC value for ulcers were the primary and first-ranked secondary end points of the trial, respectively. Results: Efficacy data were obtained from 35 participants given Bif195 and 31 given placebo. The AUC for Lewis score was significantly lower in the Bif195 group (3040 ± 1340 arbitrary units) than the placebo group (4351 ± 3195) (P =.0376). The AUC for ulcer number was significantly lower in the Bif195 group (50.4 ± 53.1 arbitrary units) than in the placebo group (75.2 ± 85.3 arbitrary units) (P =.0258). Twelve adverse events were reported from the Bif195 group and 20 from the placebo group. None of the events was determined to be related to Bif195 intake. Conclusions: In a randomized, double-blind trial of healthy volunteers, we found oral Bif195 to safely reduce the risk of small-intestinal enteropathy caused by ASA. ClinicalTrials.gov no: NCT03228589.

@article{
 title = {Habitat fragmentation is associated with dietary shifts and microbiota variability in common vampire bats},
 type = {article},
 year = {2019},
 month = {5},
 publisher = {Wiley},
 day = {9},
 id = {dda31099-6c9f-3531-b36d-81b8fdf593f6},
 created = {2025-07-07T13:25:23.358Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:09.924Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 citation_key = {Ingala2019},
 private_publication = {false},
 abstract = {This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Abstract Host ecological factors and external environmental factors are known to influence the structure of gut microbial communities, but few studies have examined the impacts of environmental changes on microbiotas in free-ranging animals. Rapid land-use change has the potential to shift gut microbial communities in wildlife through exposure to novel bacteria and/or by changing the availability or quality of local food resources. The consequences of such changes to host health and fitness remain unknown and may have important implications for pathogen spillover between humans and wildlife. To better understand the consequences of land-use change on wildlife microbiotas, we analyzed long-term dietary trends, gut microbiota composition, and innate immune function in common vampire bats (Desmodus rotundus) in two nearby sites in Belize that vary in landscape structure. We found that vampire bats living in a small forest fragment had more homogenous diets indicative of feeding on livestock and shifts in microbiota heterogeneity, but not overall composition, compared to those living in an intact forest reserve. We also found that irrespective of sampling site, vampire bats which consumed relatively more livestock showed shifts in some core bacteria compared with vampire bats which consumed relatively less livestock. The relative abundance of some core microbiota members was associated with innate immune function, suggesting that future research should consider the role of the host microbiota in immune defense and its relationship to zoonotic infection dynamics. We suggest that subsequent homogenization of diet and habitat loss through livestock rearing in the Neotropics may lead to disruption to the microbiota that could have downstream impacts on host immunity and cross-species pathogen transmission. K E Y W O R D S Desmodus rotundus, diet homogenization, land-use change, livestock, microbiota, resource provisioning},
 bibtype = {article},
 author = {Ingala, Melissa R. and Becker, Daniel J. and Bak Holm, Jacob and Kristiansen, Karsten and Simmons, Nancy B.},
 doi = {10.1002/ece3.5228},
 journal = {Ecology and Evolution}
}

This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Abstract Host ecological factors and external environmental factors are known to influence the structure of gut microbial communities, but few studies have examined the impacts of environmental changes on microbiotas in free-ranging animals. Rapid land-use change has the potential to shift gut microbial communities in wildlife through exposure to novel bacteria and/or by changing the availability or quality of local food resources. The consequences of such changes to host health and fitness remain unknown and may have important implications for pathogen spillover between humans and wildlife. To better understand the consequences of land-use change on wildlife microbiotas, we analyzed long-term dietary trends, gut microbiota composition, and innate immune function in common vampire bats (Desmodus rotundus) in two nearby sites in Belize that vary in landscape structure. We found that vampire bats living in a small forest fragment had more homogenous diets indicative of feeding on livestock and shifts in microbiota heterogeneity, but not overall composition, compared to those living in an intact forest reserve. We also found that irrespective of sampling site, vampire bats which consumed relatively more livestock showed shifts in some core bacteria compared with vampire bats which consumed relatively less livestock. The relative abundance of some core microbiota members was associated with innate immune function, suggesting that future research should consider the role of the host microbiota in immune defense and its relationship to zoonotic infection dynamics. We suggest that subsequent homogenization of diet and habitat loss through livestock rearing in the Neotropics may lead to disruption to the microbiota that could have downstream impacts on host immunity and cross-species pathogen transmission. K E Y W O R D S Desmodus rotundus, diet homogenization, land-use change, livestock, microbiota, resource provisioning

@article{
 title = {Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism},
 type = {article},
 year = {2019},
 id = {fa409164-55a2-37a7-aebb-5f7e7c021752},
 created = {2025-07-07T13:25:23.716Z},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:23.716Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Benjamin.A.H.JensenJacobB.HolmIdaS.LarsenNicolevonBurgStefanieDererAymericRivollierAnneLaureAgrinierKarolinaSulekStineA.IndrelidYkeJ.ArnoldussenSiB.SonneEvenFjæreMadsT.F.DamgaardSimoneI.PærregaardInga2019},
 private_publication = {false},
 abstract = {Interactions between host and gut microbial communities may be modulated by diets and play pivotal roles in securing immunological homeostasis and health. Here we show that intake of feed based on whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath (McB) as protein source reversed high fat high sucrose-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22°C) and at thermoneutrality (T30°C). McB feeding selectively upregulated triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small intestine and colon, and enhanced mucus production and glycosylation status suggesting improved gut health. Mice receiving McB lysates further exhibited improved glucose regulation, reduced body and liver fat along with diminished hepatic immune infiltration. Collectively, these data points towards profound whole-body effects elicited by the McB lysate suggesting that it may serve as a potent modulator of immunometabolic homeostasis.},
 bibtype = {article},
 author = {Benjamin. A. H. Jensen, Jacob B. Holm, Ida S. Larsen, Nicole von Burg, Stefanie Derer, Aymeric Rivollier, Anne Laure Agrinier, Karolina Sulek, Stine A. Indrelid, Yke J. Arnoldussen, Si B. Sonne, Even Fjære, Mads T. F. Damgaard, Simone I. Pærregaard, Inga, Tor E. Lea},
 doi = {https://doi.org/10.1101/855486},
 journal = {bioRxiv}
}

Interactions between host and gut microbial communities may be modulated by diets and play pivotal roles in securing immunological homeostasis and health. Here we show that intake of feed based on whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath (McB) as protein source reversed high fat high sucrose-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22°C) and at thermoneutrality (T30°C). McB feeding selectively upregulated triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small intestine and colon, and enhanced mucus production and glycosylation status suggesting improved gut health. Mice receiving McB lysates further exhibited improved glucose regulation, reduced body and liver fat along with diminished hepatic immune infiltration. Collectively, these data points towards profound whole-body effects elicited by the McB lysate suggesting that it may serve as a potent modulator of immunometabolic homeostasis.

@article{
 title = {Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer},
 type = {article},
 year = {2019},
 pages = {679-689},
 volume = {25},
 websites = {http://dx.doi.org/10.1038/s41591-019-0406-6},
 publisher = {Springer US},
 id = {317090a9-cede-38c1-8c2c-56cec07b99b9},
 created = {2025-07-07T13:25:24.181Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:10.341Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Wirbel2019},
 private_publication = {false},
 abstract = {Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10 −5 ). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.},
 bibtype = {article},
 author = {Wirbel, Jakob and Pyl, Paul Theodor and Kartal, Ece and Zych, Konrad and Kashani, Alireza and Milanese, Alessio and Fleck, Jonas S. and Voigt, Anita Y. and Palleja, Albert and Ponnudurai, Ruby and Sunagawa, Shinichi and Coelho, Luis Pedro and Schrotz-King, Petra and Vogtmann, Emily and Habermann, Nina and Niméus, Emma and Thomas, Andrew M. and Manghi, Paolo and Gandini, Sara and Serrano, Davide and Mizutani, Sayaka and Shiroma, Hirotsugu and Shiba, Satoshi and Shibata, Tatsuhiro and Yachida, Shinichi and Yamada, Takuji and Waldron, Levi and Naccarati, Alessio and Segata, Nicola and Sinha, Rashmi and Ulrich, Cornelia M. and Brenner, Hermann and Arumugam, Manimozhiyan and Bork, Peer and Zeller, Georg},
 doi = {10.1038/s41591-019-0406-6},
 journal = {Nature Medicine},
 number = {4}
}

Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10 −5 ). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.

@article{
 title = {Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice},
 type = {article},
 year = {2019},
 pages = {15582},
 volume = {9},
 websites = {http://www.nature.com/articles/s41598-019-52103-x},
 id = {a5d31967-b49a-3bcd-bedb-73f15f5ec20b},
 created = {2025-07-07T13:25:24.519Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:10.708Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Madsen2019},
 private_publication = {false},
 bibtype = {article},
 author = {Madsen, Mette Simone Aae and Holm, Jacob Bak and Pallejà, Albert and Wismann, Pernille and Fabricius, Katrine and Rigbolt, Kristoffer and Mikkelsen, Martin and Sommer, Morten and Jelsing, Jacob and Nielsen, Henrik Bjørn and Vrang, Niels and Hansen, Henrik H.},
 doi = {10.1038/s41598-019-52103-x},
 journal = {Scientific Reports},
 number = {1}
}

@article{
 title = {Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial},
 type = {article},
 year = {2019},
 pages = {83-93},
 volume = {68},
 id = {6788709d-bafb-3b86-9014-5f0f57769292},
 created = {2025-07-07T13:25:24.866Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:11.042Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {MunchRoager2019},
 private_publication = {false},
 abstract = {Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.},
 bibtype = {article},
 author = {Munch Roager, Henrik and Vogt, Josef K. and Kristensen, Mette and Hansen, Lea Benedicte S. and Ibrügger, Sabine and Maerkedahl, Rasmus B. and Bahl, Martin Iain and Lind, Mads Vendelbo and Nielsen, Rikke L. and Frøkiaer, Hanne and Gøbel, Rikke Juul and Landberg, Rikard and Ross, Alastair B. and Brix, Susanne and Holck, Jesper and Meyer, Anne S. and Sparholt, Morten H. and Christensen, Anders F. and Carvalho, Vera and Hartmann, Bolette and Holst, Jens Juul and Rumessen, Jüri Johannes and Linneberg, Allan and Sicheritz-Pontén, Thomas and Dalgaard, Marlene D. and Blennow, Andreas and Frandsen, Henrik Lauritz and Villas-Bôas, Silas and Kristiansen, Karsten and Vestergaard, Henrik and Hansen, Torben and Ekstrøm, Claus T. and Ritz, Christian and Nielsen, Henrik Bjørn and Pedersen, Oluf Borbye and Gupta, Ramneek and Lauritzen, Lotte and Licht, Tine Rask},
 doi = {10.1136/gutjnl-2017-314786},
 journal = {Gut},
 number = {1}
}

Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.

@article{
 title = {Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice},
 type = {article},
 year = {2019},
 volume = {9},
 month = {12},
 publisher = {Nature Publishing Group},
 day = {1},
 id = {85c45348-bb0d-38e1-a344-3dca931840b6},
 created = {2025-10-30T12:09:26.811Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:30.926Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09–145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.},
 bibtype = {article},
 author = {Madsen, Mette Simone Aae and Holm, Jacob Bak and Pallejà, Albert and Wismann, Pernille and Fabricius, Katrine and Rigbolt, Kristoffer and Mikkelsen, Martin and Sommer, Morten and Jelsing, Jacob and Nielsen, Henrik Bjørn and Vrang, Niels and Hansen, Henrik H.},
 doi = {10.1038/s41598-019-52103-x},
 journal = {Scientific Reports},
 number = {1}
}

Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09–145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.

@article{
 title = {Bifidobacterium breve Bif195 Protects Against Small-Intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers},
 type = {article},
 year = {2019},
 keywords = {Aspirin,Bacteria,Bleeding,Microbiota},
 pages = {637-646.e4},
 volume = {157},
 month = {9},
 publisher = {W.B. Saunders},
 day = {1},
 id = {c49dd364-efa0-37c0-924f-a2fc5c58aabb},
 created = {2025-10-30T12:09:26.813Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:29.442Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background & Aims: Enteropathy and small-intestinal ulcers are common adverse effects of nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA). Safe, cytoprotective strategies are needed to reduce this risk. Specific bifidobacteria might have cytoprotective activities, but little is known about these effects in humans. We used serial video capsule endoscopy (VCE) to assess the efficacy of a specific Bifidobacterium strain in healthy volunteers exposed to ASA. Methods: We performed a single-site, double-blind, parallel-group, proof-of-concept analysis of 75 heathy volunteers given ASA (300 mg) daily for 6 weeks, from July 31 through October 24, 2017. The participants were randomly assigned (1:1) to groups given oral capsules of Bifidobacterium breve (Bif195) (≥5 × 1010 colony-forming units) or placebo daily for 8 weeks. Small-intestinal damage was analyzed by serial VCE at 6 visits. The area under the curve (AUC) for intestinal damage (Lewis score) and the AUC value for ulcers were the primary and first-ranked secondary end points of the trial, respectively. Results: Efficacy data were obtained from 35 participants given Bif195 and 31 given placebo. The AUC for Lewis score was significantly lower in the Bif195 group (3040 ± 1340 arbitrary units) than the placebo group (4351 ± 3195) (P =.0376). The AUC for ulcer number was significantly lower in the Bif195 group (50.4 ± 53.1 arbitrary units) than in the placebo group (75.2 ± 85.3 arbitrary units) (P =.0258). Twelve adverse events were reported from the Bif195 group and 20 from the placebo group. None of the events was determined to be related to Bif195 intake. Conclusions: In a randomized, double-blind trial of healthy volunteers, we found oral Bif195 to safely reduce the risk of small-intestinal enteropathy caused by ASA. ClinicalTrials.gov no: NCT03228589.},
 bibtype = {article},
 author = {Mortensen, Brynjulf and Murphy, Clodagh and O'Grady, John and Lucey, Mary and Elsafi, Gafer and Barry, Lillian and Westphal, Vibeke and Wellejus, Anja and Lukjancenko, Oksana and Eklund, Aron C. and Nielsen, Henrik Bjørn and Baker, Adam and Damholt, Anders and van Hylckama Vlieg, Johan E.T. and Shanahan, Fergus and Buckley, Martin},
 doi = {10.1053/j.gastro.2019.05.008},
 journal = {Gastroenterology},
 number = {3}
}

Background & Aims: Enteropathy and small-intestinal ulcers are common adverse effects of nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA). Safe, cytoprotective strategies are needed to reduce this risk. Specific bifidobacteria might have cytoprotective activities, but little is known about these effects in humans. We used serial video capsule endoscopy (VCE) to assess the efficacy of a specific Bifidobacterium strain in healthy volunteers exposed to ASA. Methods: We performed a single-site, double-blind, parallel-group, proof-of-concept analysis of 75 heathy volunteers given ASA (300 mg) daily for 6 weeks, from July 31 through October 24, 2017. The participants were randomly assigned (1:1) to groups given oral capsules of Bifidobacterium breve (Bif195) (≥5 × 1010 colony-forming units) or placebo daily for 8 weeks. Small-intestinal damage was analyzed by serial VCE at 6 visits. The area under the curve (AUC) for intestinal damage (Lewis score) and the AUC value for ulcers were the primary and first-ranked secondary end points of the trial, respectively. Results: Efficacy data were obtained from 35 participants given Bif195 and 31 given placebo. The AUC for Lewis score was significantly lower in the Bif195 group (3040 ± 1340 arbitrary units) than the placebo group (4351 ± 3195) (P =.0376). The AUC for ulcer number was significantly lower in the Bif195 group (50.4 ± 53.1 arbitrary units) than in the placebo group (75.2 ± 85.3 arbitrary units) (P =.0258). Twelve adverse events were reported from the Bif195 group and 20 from the placebo group. None of the events was determined to be related to Bif195 intake. Conclusions: In a randomized, double-blind trial of healthy volunteers, we found oral Bif195 to safely reduce the risk of small-intestinal enteropathy caused by ASA. ClinicalTrials.gov no: NCT03228589.

@article{
 title = {Habitat fragmentation is associated with dietary shifts and microbiota variability in common vampire bats.},
 type = {article},
 year = {2019},
 keywords = {Desmodus rotundus,diet homogenization,land‐use change,livestock,microbiota,resource provisioning},
 pages = {6508-6523},
 volume = {9},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/31236240,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6580296},
 month = {6},
 publisher = {John Wiley and Sons Ltd},
 day = {1},
 id = {ef787f0f-f85b-3618-9ce4-53a9253bab65},
 created = {2025-10-30T12:09:26.815Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:26.815Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Host ecological factors and external environmental factors are known to influence the structure of gut microbial communities, but few studies have examined the impacts of environmental changes on microbiotas in free-ranging animals. Rapid land-use change has the potential to shift gut microbial communities in wildlife through exposure to novel bacteria and/or by changing the availability or quality of local food resources. The consequences of such changes to host health and fitness remain unknown and may have important implications for pathogen spillover between humans and wildlife. To better understand the consequences of land-use change on wildlife microbiotas, we analyzed long-term dietary trends, gut microbiota composition, and innate immune function in common vampire bats (Desmodus rotundus) in two nearby sites in Belize that vary in landscape structure. We found that vampire bats living in a small forest fragment had more homogenous diets indicative of feeding on livestock and shifts in microbiota heterogeneity, but not overall composition, compared to those living in an intact forest reserve. We also found that irrespective of sampling site, vampire bats which consumed relatively more livestock showed shifts in some core bacteria compared with vampire bats which consumed relatively less livestock. The relative abundance of some core microbiota members was associated with innate immune function, suggesting that future research should consider the role of the host microbiota in immune defense and its relationship to zoonotic infection dynamics. We suggest that subsequent homogenization of diet and habitat loss through livestock rearing in the Neotropics may lead to disruption to the microbiota that could have downstream impacts on host immunity and cross-species pathogen transmission.},
 bibtype = {article},
 author = {Ingala, Melissa R and Becker, Daniel J and Bak Holm, Jacob and Kristiansen, Karsten and Simmons, Nancy B},
 doi = {10.1002/ece3.5228},
 journal = {Ecology and evolution},
 number = {11}
}

Host ecological factors and external environmental factors are known to influence the structure of gut microbial communities, but few studies have examined the impacts of environmental changes on microbiotas in free-ranging animals. Rapid land-use change has the potential to shift gut microbial communities in wildlife through exposure to novel bacteria and/or by changing the availability or quality of local food resources. The consequences of such changes to host health and fitness remain unknown and may have important implications for pathogen spillover between humans and wildlife. To better understand the consequences of land-use change on wildlife microbiotas, we analyzed long-term dietary trends, gut microbiota composition, and innate immune function in common vampire bats (Desmodus rotundus) in two nearby sites in Belize that vary in landscape structure. We found that vampire bats living in a small forest fragment had more homogenous diets indicative of feeding on livestock and shifts in microbiota heterogeneity, but not overall composition, compared to those living in an intact forest reserve. We also found that irrespective of sampling site, vampire bats which consumed relatively more livestock showed shifts in some core bacteria compared with vampire bats which consumed relatively less livestock. The relative abundance of some core microbiota members was associated with innate immune function, suggesting that future research should consider the role of the host microbiota in immune defense and its relationship to zoonotic infection dynamics. We suggest that subsequent homogenization of diet and habitat loss through livestock rearing in the Neotropics may lead to disruption to the microbiota that could have downstream impacts on host immunity and cross-species pathogen transmission.

@article{
 title = {Increased abundance of proteobacteria in aggressive Crohn’s disease seven years after diagnosis},
 type = {article},
 year = {2019},
 volume = {9},
 month = {12},
 publisher = {Nature Publishing Group},
 day = {1},
 id = {e41ebcb5-ef10-3b73-9309-2946d07ad03c},
 created = {2025-10-30T12:09:26.827Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:31.321Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Intestinal dysbiosis in inflammatory bowel disease (IBD) patients depend on disease activity. We aimed to characterize the microbiota after 7 years of follow-up in an unselected cohort of IBD patients according to disease activity and disease severity. Fifty eight Crohn’s disease (CD) and 82 ulcerative colitis (UC) patients were included. Disease activity was assessed by the Harvey-Bradshaw Index for CD and Simple Clinical Colitis Activity Index for UC. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. In UC patients with active disease and in CD patients with aggressive disease the richness (number of OTUs, p = 0.018 and p = 0.013, respectively) and diversity (Shannons index, p = 0.017 and p = 0.023, respectively) were significantly decreased. In the active UC group there was a significant decrease in abundance of the phylum Firmicutes (p = 0.018). The same was found in CD patients with aggressive disease (p = 0.05) while the abundance of Proteobacteria phylum showed a significant increase (p = 0.03) in CD patients. We found a change in the microbial abundance in UC patients with active disease and in CD patients with aggressive disease. These results suggest that dysbiosis of the gut in IBD patients is not only related to current activity but also to the course of the disease.},
 bibtype = {article},
 author = {Vester-Andersen, M. K. and Mirsepasi-Lauridsen, H. C. and Prosberg, M. V. and Mortensen, C. O. and Träger, C. and Skovsen, K. and Thorkilgaard, T. and Nøjgaard, C. and Vind, I. and Krogfelt, K. A. and Sørensen, N. and Bendtsen, F. and Petersen, A. M.},
 doi = {10.1038/s41598-019-49833-3},
 journal = {Scientific Reports},
 number = {1}
}

Intestinal dysbiosis in inflammatory bowel disease (IBD) patients depend on disease activity. We aimed to characterize the microbiota after 7 years of follow-up in an unselected cohort of IBD patients according to disease activity and disease severity. Fifty eight Crohn’s disease (CD) and 82 ulcerative colitis (UC) patients were included. Disease activity was assessed by the Harvey-Bradshaw Index for CD and Simple Clinical Colitis Activity Index for UC. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. In UC patients with active disease and in CD patients with aggressive disease the richness (number of OTUs, p = 0.018 and p = 0.013, respectively) and diversity (Shannons index, p = 0.017 and p = 0.023, respectively) were significantly decreased. In the active UC group there was a significant decrease in abundance of the phylum Firmicutes (p = 0.018). The same was found in CD patients with aggressive disease (p = 0.05) while the abundance of Proteobacteria phylum showed a significant increase (p = 0.03) in CD patients. We found a change in the microbial abundance in UC patients with active disease and in CD patients with aggressive disease. These results suggest that dysbiosis of the gut in IBD patients is not only related to current activity but also to the course of the disease.

@article{
 title = {Gut microbiota composition in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives},
 type = {article},
 year = {2019},
 keywords = {Bipolar disorder,Gut microbiota,Microbiota,Newly diagnosed,Unaffected relatives},
 pages = {112-118},
 volume = {75},
 month = {1},
 publisher = {Academic Press Inc.},
 day = {1},
 id = {7a6339b9-aa37-3c79-be5f-8b2abd516bdb},
 created = {2025-10-30T12:09:26.840Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:29.574Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Objective: An aberrant gut microbiota may be associated with a broad spectrum of diseases including mental illness. The gut microbiota is scarcely studied in bipolar disorder (BD). We examined the gut microbiota composition in patients with newly diagnosed BD, their unaffected first-degree relatives and healthy individuals. Methods: Stool samples were collected from 113 patients with BD, 39 unaffected first-degree relatives and 77 healthy individuals and the microbiota was profiled using 16S rRNA gene amplicon sequencing. Results: The gut microbiota community membership of patients with BD differed from that of healthy individuals (R2 = 1.0%, P = 0.008), whereas the community membership of unaffected first-degree relatives did not. Flavonifractor was present in 61% of patients with BD, 42% of their unaffected relatives and 39% of healthy individuals. Presence of Flavonifractor was associated with an odds ratio of 2.9 (95%CI: 1.6–5.2, P = 5.8 × 10−4, Q = 0.036) for having BD. When excluding smokers, presence of Flavonifractor was associated with an odds ratio of 2.3 (95%CI: 1.1–5.3, P = 0.019) for having BD. However, when considering the subsample of non-smokers only, BD and presence of Flavonifractor were no longer associated when adjusted for all possible tests at genus level (Q = 0.6). Presence of Flavonifractor in patients with BD was associated with smoking and female sex, but not with age, waist circumference, exercise level, high-sensitive C-reactive protein, current affective state, subtype of BD, illness duration or psychotropic medication, respectively. Conclusion: Flavonifractor, a bacterial genus that may induce oxidative stress and inflammation in its host, was associated with BD. Higher prevalence of smoking among patients with BD contributed to our findings, and it cannot be excluded that findings are influenced by residual confounding.},
 bibtype = {article},
 author = {Coello, Klara and Hansen, Tue Haldor and Sørensen, Nikolaj and Munkholm, Klaus and Kessing, Lars Vedel and Pedersen, Oluf and Vinberg, Maj},
 doi = {10.1016/j.bbi.2018.09.026},
 journal = {Brain, Behavior, and Immunity}
}

Objective: An aberrant gut microbiota may be associated with a broad spectrum of diseases including mental illness. The gut microbiota is scarcely studied in bipolar disorder (BD). We examined the gut microbiota composition in patients with newly diagnosed BD, their unaffected first-degree relatives and healthy individuals. Methods: Stool samples were collected from 113 patients with BD, 39 unaffected first-degree relatives and 77 healthy individuals and the microbiota was profiled using 16S rRNA gene amplicon sequencing. Results: The gut microbiota community membership of patients with BD differed from that of healthy individuals (R2 = 1.0%, P = 0.008), whereas the community membership of unaffected first-degree relatives did not. Flavonifractor was present in 61% of patients with BD, 42% of their unaffected relatives and 39% of healthy individuals. Presence of Flavonifractor was associated with an odds ratio of 2.9 (95%CI: 1.6–5.2, P = 5.8 × 10−4, Q = 0.036) for having BD. When excluding smokers, presence of Flavonifractor was associated with an odds ratio of 2.3 (95%CI: 1.1–5.3, P = 0.019) for having BD. However, when considering the subsample of non-smokers only, BD and presence of Flavonifractor were no longer associated when adjusted for all possible tests at genus level (Q = 0.6). Presence of Flavonifractor in patients with BD was associated with smoking and female sex, but not with age, waist circumference, exercise level, high-sensitive C-reactive protein, current affective state, subtype of BD, illness duration or psychotropic medication, respectively. Conclusion: Flavonifractor, a bacterial genus that may induce oxidative stress and inflammation in its host, was associated with BD. Higher prevalence of smoking among patients with BD contributed to our findings, and it cannot be excluded that findings are influenced by residual confounding.

@article{
 title = {Vitamin D and phenylbutyrate supplementation does not modulate gut derived immune activation in HIV-1},
 type = {article},
 year = {2019},
 keywords = {Clinical trial,HIV-1,Kynurenine/tryptophan ratio,LL-37,Microbiota,Phenylbutyrate,TMAO,Vitamin D},
 volume = {11},
 month = {7},
 publisher = {MDPI AG},
 day = {1},
 id = {f851c513-76a3-3c4e-863f-551c49b95ba4},
 created = {2025-10-30T12:09:26.855Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:30.371Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals (n = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.gov NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels (p < 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insuffcient subjects demonstrated a significant increase of LL-37 in the treatment group (p = 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units (p = 0.71), Shannon microbial diversity index (p = 0.82), or in principal component analyses (p = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.},
 bibtype = {article},
 author = {Missailidis, Catharina and Sørensen, Nikolaj and Ashenafi, Senait and Amogne, Wondwossen and Kassa, Endale and Bekele, Amsalu and Getachew, Meron and Gebreselassie, Nebiat and Aseffa, Abraham and Aderaye, Getachew and Andersson, Jan and Brighenti, Susanna and Bergman, Peter},
 doi = {10.3390/nu11071675},
 journal = {Nutrients},
 number = {7}
}

Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals (n = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.gov NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels (p < 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insuffcient subjects demonstrated a significant increase of LL-37 in the treatment group (p = 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units (p = 0.71), Shannon microbial diversity index (p = 0.82), or in principal component analyses (p = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.

@article{
 title = {Mechanisms Preserving Insulin Action during High Dietary Fat Intake},
 type = {article},
 year = {2019},
 keywords = {de novo lipogenesis,dietary fat,hepatic glucose production,insulin sensitivity,insulin signaling,lipoprotein metabolism,liver,metabolic regulation,skeletal muscle,substrate oxidation},
 pages = {50-63.e4},
 volume = {29},
 month = {1},
 publisher = {Cell Press},
 day = {8},
 id = {ffeee4ab-6e06-31a6-8ebc-e1c6f587a3b3},
 created = {2025-10-30T12:09:26.856Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:30.638Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Prolonged intervention studies investigating molecular metabolism are necessary for a deeper understanding of dietary effects on health. Here we provide mechanistic information about metabolic adaptation to fat-rich diets. Healthy, slightly overweight men ingested saturated or polyunsaturated fat-rich diets for 6 weeks during weight maintenance. Hyperinsulinemic clamps combined with leg balance technique revealed unchanged peripheral insulin sensitivity, independent of fatty acid type. Both diets increased fat oxidation potential in muscle. Hepatic insulin clearance increased, while glucose production, de novo lipogenesis, and plasma triacylglycerol decreased. High fat intake changed the plasma proteome in the immune-supporting direction and the gut microbiome displayed changes at taxonomical and functional level with polyunsaturated fatty acid (PUFA). In mice, eucaloric feeding of human PUFA and saturated fatty acid diets lowered hepatic triacylglycerol content compared with low-fat-fed control mice, and induced adaptations in the liver supportive of decreased gluconeogenesis and lipogenesis. Intake of fat-rich diets thus induces extensive metabolic adaptations enabling disposition of dietary fat without metabolic complications.},
 bibtype = {article},
 author = {Lundsgaard, Anne Marie and Holm, Jacob B. and Sjøberg, Kim A. and Bojsen-Møller, Kirstine N. and Myrmel, Lene S. and Fjære, Even and Jensen, Benjamin A.H. and Nicolaisen, Trine S. and Hingst, Janne R. and Hansen, Sine L. and Doll, Sophia and Geyer, Philip E. and Deshmukh, Atul S. and Holst, Jens J. and Madsen, Lise and Kristiansen, Karsten and Wojtaszewski, Jørgen F.P. and Richter, Erik A. and Kiens, Bente},
 doi = {10.1016/j.cmet.2018.08.022},
 journal = {Cell Metabolism},
 number = {1}
}

Prolonged intervention studies investigating molecular metabolism are necessary for a deeper understanding of dietary effects on health. Here we provide mechanistic information about metabolic adaptation to fat-rich diets. Healthy, slightly overweight men ingested saturated or polyunsaturated fat-rich diets for 6 weeks during weight maintenance. Hyperinsulinemic clamps combined with leg balance technique revealed unchanged peripheral insulin sensitivity, independent of fatty acid type. Both diets increased fat oxidation potential in muscle. Hepatic insulin clearance increased, while glucose production, de novo lipogenesis, and plasma triacylglycerol decreased. High fat intake changed the plasma proteome in the immune-supporting direction and the gut microbiome displayed changes at taxonomical and functional level with polyunsaturated fatty acid (PUFA). In mice, eucaloric feeding of human PUFA and saturated fatty acid diets lowered hepatic triacylglycerol content compared with low-fat-fed control mice, and induced adaptations in the liver supportive of decreased gluconeogenesis and lipogenesis. Intake of fat-rich diets thus induces extensive metabolic adaptations enabling disposition of dietary fat without metabolic complications.

@article{
 title = {Remitted affective disorders and high familial risk of affective disorders associate with aberrant intestinal microbiota},
 type = {article},
 year = {2019},
 keywords = {affective disorder,human microbiome,twins monozygotic},
 pages = {174-184},
 volume = {139},
 month = {2},
 publisher = {Blackwell Publishing Ltd},
 day = {1},
 id = {f99abb59-27cb-3404-b90c-816d75580209},
 created = {2025-10-30T12:09:26.860Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:26.860Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Objective: Affective disorders seem associated with aberrant intestinal microbiota but whether this pattern also occurs in individuals at increased heritable risk is unknown. We investigated associations between gut microbiota profiles and affective disorders by comparing monozygotic (MZ) twins concordant (affected twins with unipolar or bipolar disorder in remission) and discordant to affective disorders (high-risk) with MZ twins without affective disorders (low-risk). Methods: Stool samples were collected from 128 MZ twins and the microbiome was profiled using 16S rDNA sequencing of the V3–V4 region. Results: Affected twins had a lower diversity and an absence of a specific operational taxonomical unit (OTU) in comparison with low-risk twins. The high-risk twins exhibited the same pattern although the lower diversity was only at a trend level. The OTU belonged to the family Christensenellaceae. The findings were not explained by lifestyle factors (smoking, alcohol consumption, body mass index, or psychotropic medication). Conclusion: Affected twins in remission and high-risk twins presented aberrant gut microbiota with depletion of a specific OTU. If replicated, this reduced relative sequence absence may together with the globally altered microbiota composition act as a vulnerability marker by accentuating the effect of gene–environment interactions in individuals genetically disposed for an affective disorder.},
 bibtype = {article},
 author = {Vinberg, M. and Ottesen, N. M. and Meluken, I. and Sørensen, N. and Pedersen, O. and Kessing, L. V. and Miskowiak, K. W.},
 doi = {10.1111/acps.12976},
 journal = {Acta Psychiatrica Scandinavica},
 number = {2}
}

Objective: Affective disorders seem associated with aberrant intestinal microbiota but whether this pattern also occurs in individuals at increased heritable risk is unknown. We investigated associations between gut microbiota profiles and affective disorders by comparing monozygotic (MZ) twins concordant (affected twins with unipolar or bipolar disorder in remission) and discordant to affective disorders (high-risk) with MZ twins without affective disorders (low-risk). Methods: Stool samples were collected from 128 MZ twins and the microbiome was profiled using 16S rDNA sequencing of the V3–V4 region. Results: Affected twins had a lower diversity and an absence of a specific operational taxonomical unit (OTU) in comparison with low-risk twins. The high-risk twins exhibited the same pattern although the lower diversity was only at a trend level. The OTU belonged to the family Christensenellaceae. The findings were not explained by lifestyle factors (smoking, alcohol consumption, body mass index, or psychotropic medication). Conclusion: Affected twins in remission and high-risk twins presented aberrant gut microbiota with depletion of a specific OTU. If replicated, this reduced relative sequence absence may together with the globally altered microbiota composition act as a vulnerability marker by accentuating the effect of gene–environment interactions in individuals genetically disposed for an affective disorder.

@article{
 title = {Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial},
 type = {article},
 year = {2019},
 pages = {83-93},
 volume = {68},
 month = {1},
 publisher = {BMJ Publishing Group},
 day = {1},
 id = {7e2eb973-0b7c-32e9-aa24-8a90c9175024},
 created = {2025-10-30T12:09:26.892Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:30.898Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.},
 bibtype = {article},
 author = {Munch Roager, Henrik and Vogt, Josef K. and Kristensen, Mette and Hansen, Lea Benedicte S. and Ibrügger, Sabine and Maerkedahl, Rasmus B. and Bahl, Martin Iain and Lind, Mads Vendelbo and Nielsen, Rikke L. and Frøkiaer, Hanne and Gøbel, Rikke Juul and Landberg, Rikard and Ross, Alastair B. and Brix, Susanne and Holck, Jesper and Meyer, Anne S. and Sparholt, Morten H. and Christensen, Anders F. and Carvalho, Vera and Hartmann, Bolette and Holst, Jens Juul and Rumessen, Jüri Johannes and Linneberg, Allan and Sicheritz-Pontén, Thomas and Dalgaard, Marlene D. and Blennow, Andreas and Frandsen, Henrik Lauritz and Villas-Bôas, Silas and Kristiansen, Karsten and Vestergaard, Henrik and Hansen, Torben and Ekstrøm, Claus T. and Ritz, Christian and Nielsen, Henrik Bjørn and Pedersen, Oluf Borbye and Gupta, Ramneek and Lauritzen, Lotte and Licht, Tine Rask},
 doi = {10.1136/gutjnl-2017-314786},
 journal = {Gut},
 number = {1}
}

Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.

@article{
 title = {Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice},
 type = {article},
 year = {2019},
 keywords = {Diet-induced obesity,Host-microbe interactions,Human defensins,Insulin resistance,NAFLD},
 pages = {E42-E52},
 volume = {317},
 publisher = {American Physiological Society},
 id = {2d864af1-a8fd-3913-92c2-7a42d9fde941},
 created = {2025-10-30T12:09:26.954Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:30.292Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Overnutrition is the principal cause of insulin resis-tance (IR) and dyslipidemia, which drive nonalcoholic fatty liver disease (NAFLD). Overnutrition is further linked to disrupted bowel function, microbiota alterations, and change of function in gut-lining cell populations, including Paneth cells of the small intestine. Paneth cells regulate microbial diversity through expression of antimicrobial peptides, particularly human α-defensin-5 (HD-5), and have shown repressed secretory capacity in human obesity. Mice were fed a 60% high-fat diet for 13 wk and subsequently treated with physiologically relevant amounts of HD-5 (0.001%) or vehicle for 10 wk. The glucoregulatory capacity was determined by glucose tolerance tests and measurements of corresponding insulin concentrations both before and during intervention. Gut microbiome composition was examined by 16S rRNA gene amplicon sequencing. HD-5-treated mice exhibited improved glucoregulatory capacity along with an ameliorated plasma and liver lipid profile. This was accompanied by specific decrease in jejunal inflammation and gut microbiota alterations including increased Bifidobacterium abundances, which correlated inversely with metabolic dysfunctions. This study provides proof of concept for the use of human defensins to improve host metabolism by mitigating the triad cluster of dyslipidemia, IR, and NAFLD.},
 bibtype = {article},
 author = {Larsen, Ida Søgaard and Fritzen, Andreas Mæchel and Carl, Christian Strini and Agerholm, Marianne and Damgaard, Mads Thue Fejerskov and Holm, Jacob Bak and Marette, André and Nordkild, Peter and Kiens, Bente and Kristiansen, Karsten and Wehkamp, Jan and Jensen, Benjamin Anderschou Holbech},
 doi = {10.1152/ajpendo.00019.2019},
 journal = {American Journal of Physiology - Endocrinology and Metabolism},
 number = {1}
}

Overnutrition is the principal cause of insulin resis-tance (IR) and dyslipidemia, which drive nonalcoholic fatty liver disease (NAFLD). Overnutrition is further linked to disrupted bowel function, microbiota alterations, and change of function in gut-lining cell populations, including Paneth cells of the small intestine. Paneth cells regulate microbial diversity through expression of antimicrobial peptides, particularly human α-defensin-5 (HD-5), and have shown repressed secretory capacity in human obesity. Mice were fed a 60% high-fat diet for 13 wk and subsequently treated with physiologically relevant amounts of HD-5 (0.001%) or vehicle for 10 wk. The glucoregulatory capacity was determined by glucose tolerance tests and measurements of corresponding insulin concentrations both before and during intervention. Gut microbiome composition was examined by 16S rRNA gene amplicon sequencing. HD-5-treated mice exhibited improved glucoregulatory capacity along with an ameliorated plasma and liver lipid profile. This was accompanied by specific decrease in jejunal inflammation and gut microbiota alterations including increased Bifidobacterium abundances, which correlated inversely with metabolic dysfunctions. This study provides proof of concept for the use of human defensins to improve host metabolism by mitigating the triad cluster of dyslipidemia, IR, and NAFLD.

@article{
 title = {Heterologous expression of intact biosynthetic gene clusters in Fusarium graminearum},
 type = {article},
 year = {2019},
 keywords = {Cytokinin,Fusarium,Heterologous expression,Lipopeptides,Non-ribosomal peptides,Secondary metabolites},
 volume = {132},
 month = {11},
 publisher = {Academic Press Inc.},
 day = {1},
 id = {4070224d-a90c-3615-8b8e-1cdf29e2fb5c},
 created = {2025-10-30T12:18:14.052Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:18:16.404Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Filamentous fungi such as species from the genus Fusarium are capable of producing a wide palette of interesting metabolites relevant to health, agriculture and biotechnology. Secondary metabolites are formed from large synthase/synthetase enzymes often encoded in gene clusters containing additional enzymes cooperating in the metabolite's biosynthesis. The true potential of fungal metabolomes remain untapped as the majority of secondary metabolite gene clusters are silent under standard laboratory growth conditions. One way to achieve expression of biosynthetic pathways is to clone the responsible genes and express them in a well-suited heterologous host, which poses a challenge since Fusarium polyketide synthase and non-ribosomal peptide synthetase gene clusters can be large (e.g. as large as 80 kb) and comprise several genes necessary for product formation. The major challenge associated with heterologous expression of fungal biosynthesis pathways is thus handling and cloning large DNA sequences. In this paper we present the successful workflow for cloning, reconstruction and heterologous production of two previously characterized Fusarium pseudograminearum natural product pathways in Fusarium graminearum. In vivo yeast recombination enabled rapid assembly of the W493 (NRPS32-PKS40) and the Fusarium Cytokinin gene clusters. F. graminearum transformants were obtained through protoplast-mediated and Agrobacterium tumefaciens-mediated transformation. Whole genome sequencing revealed isolation of transformants carrying intact copies the gene clusters was possible. Known Fusarium cytokinin metabolites; fusatin, 8-oxo-fusatin, 8-oxo-isopentenyladenine, fusatinic acid together with cis– and trans-zeatin were detected by liquid chromatography and mass spectrometry, which confirmed gene functionality in F. graminearum. In addition the non-ribosomal lipopeptide products W493 A and B was heterologously produced in similar amounts to that observed in the F. pseudograminearum doner. The Fusarium pan-genome comprises more than 60 uncharacterized putative secondary metabolite gene clusters. We nominate the well-characterized F. graminearum as a heterologous expression platform for Fusarium secondary metabolite gene clusters, and present our experience cloning and introducing gene clusters into this species. We expect the presented methods will inspire future endevours in heterologous production of Fusarium metabolites and potentially aid the production and characterization of novel natural products.},
 bibtype = {article},
 author = {Nielsen, Mikkel Rank and Wollenberg, Rasmus Dam and Westphal, Klaus Ringsborg and Sondergaard, Teis Esben and Wimmer, Reinhard and Gardiner, Donald Max and Sørensen, Jens Laurids},
 doi = {10.1016/j.fgb.2019.103248},
 journal = {Fungal Genetics and Biology}
}

Filamentous fungi such as species from the genus Fusarium are capable of producing a wide palette of interesting metabolites relevant to health, agriculture and biotechnology. Secondary metabolites are formed from large synthase/synthetase enzymes often encoded in gene clusters containing additional enzymes cooperating in the metabolite's biosynthesis. The true potential of fungal metabolomes remain untapped as the majority of secondary metabolite gene clusters are silent under standard laboratory growth conditions. One way to achieve expression of biosynthetic pathways is to clone the responsible genes and express them in a well-suited heterologous host, which poses a challenge since Fusarium polyketide synthase and non-ribosomal peptide synthetase gene clusters can be large (e.g. as large as 80 kb) and comprise several genes necessary for product formation. The major challenge associated with heterologous expression of fungal biosynthesis pathways is thus handling and cloning large DNA sequences. In this paper we present the successful workflow for cloning, reconstruction and heterologous production of two previously characterized Fusarium pseudograminearum natural product pathways in Fusarium graminearum. In vivo yeast recombination enabled rapid assembly of the W493 (NRPS32-PKS40) and the Fusarium Cytokinin gene clusters. F. graminearum transformants were obtained through protoplast-mediated and Agrobacterium tumefaciens-mediated transformation. Whole genome sequencing revealed isolation of transformants carrying intact copies the gene clusters was possible. Known Fusarium cytokinin metabolites; fusatin, 8-oxo-fusatin, 8-oxo-isopentenyladenine, fusatinic acid together with cis– and trans-zeatin were detected by liquid chromatography and mass spectrometry, which confirmed gene functionality in F. graminearum. In addition the non-ribosomal lipopeptide products W493 A and B was heterologously produced in similar amounts to that observed in the F. pseudograminearum doner. The Fusarium pan-genome comprises more than 60 uncharacterized putative secondary metabolite gene clusters. We nominate the well-characterized F. graminearum as a heterologous expression platform for Fusarium secondary metabolite gene clusters, and present our experience cloning and introducing gene clusters into this species. We expect the presented methods will inspire future endevours in heterologous production of Fusarium metabolites and potentially aid the production and characterization of novel natural products.

@article{
 title = {Oral metallo-beta-lactamase protects the gut microbiome from carbapenem-mediated damage and reduces propagation of antibiotic resistance in pigs},
 type = {article},
 year = {2019},
 keywords = {Antibiotic resistance,Beta-lactamase,Dysbiosis,Gut microbiome,Porcine (pig) model},
 volume = {10},
 publisher = {Frontiers Media S.A.},
 id = {e571ec56-ec07-3d21-bdc7-0df9a117c65b},
 created = {2025-10-30T12:26:00.970Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:08.377Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Antibiotics can damage the gut microbiome, leading to serious adventitious infections and emergence of antibiotic resistant pathogens. Antibiotic inactivation in the GI tract represents a strategy to protect colonic microbiota integrity and reduce antibiotic resistance. Clinical utility of this approach was established when SYN-004 (ribaxamase), an orally-administered beta-lactamase, was demonstrated to degrade ceftriaxone in the GI tract and preserve the gut microbiome. Ribaxamase degrades penicillins and cephalosporin beta-lactams, but not carbapenems. To expand this prophylactic approach to include all classes of beta-lactam antibiotics, a novel carbapenemase, formulated for oral administration, SYN-006, was evaluated in a porcine model of antibiotic-mediated gut dysbiosis. Pigs (20 kg, n = 16) were treated with the carbapenem, ertapenem (ERT), (IV, 30 mg/kg, SID) for 4 days and a cohort (n = 8) also received SYN-006 (PO, 50 mg, QID), beginning the day before antibiotic administration. ERT serum levels were not statistically different in ERT and ERT + SYN-006 groups, indicating that SYN-006 did not alter systemic antibiotic levels. Microbiomes were evaluated using whole genome shotgun metagenomics analyses of fecal DNA collected prior to and after antibiotic treatment. ERT caused significant changes to the gut microbiome that were mitigated in the presence of SYN-006. In addition, SYN-006 attenuated emergence of antibiotic resistance, including encoded beta-lactamases and genes conferring resistance to a broad range of antibiotics such as aminoglycosides and macrolides. SYN-006 has the potential to become the first therapy designed to protect the gut microbiome from all classes of beta-lactam antibiotics and reduce emergence of carbapenem-resistant pathogens.},
 bibtype = {article},
 author = {Connelly, Sheila and Fanelli, Brian and Hasan, Nur A. and Colwell, Rita R. and Kaleko, Michael},
 doi = {10.3389/FMICB.2019.00101},
 journal = {Frontiers in Microbiology},
 number = {FEB}
}

Antibiotics can damage the gut microbiome, leading to serious adventitious infections and emergence of antibiotic resistant pathogens. Antibiotic inactivation in the GI tract represents a strategy to protect colonic microbiota integrity and reduce antibiotic resistance. Clinical utility of this approach was established when SYN-004 (ribaxamase), an orally-administered beta-lactamase, was demonstrated to degrade ceftriaxone in the GI tract and preserve the gut microbiome. Ribaxamase degrades penicillins and cephalosporin beta-lactams, but not carbapenems. To expand this prophylactic approach to include all classes of beta-lactam antibiotics, a novel carbapenemase, formulated for oral administration, SYN-006, was evaluated in a porcine model of antibiotic-mediated gut dysbiosis. Pigs (20 kg, n = 16) were treated with the carbapenem, ertapenem (ERT), (IV, 30 mg/kg, SID) for 4 days and a cohort (n = 8) also received SYN-006 (PO, 50 mg, QID), beginning the day before antibiotic administration. ERT serum levels were not statistically different in ERT and ERT + SYN-006 groups, indicating that SYN-006 did not alter systemic antibiotic levels. Microbiomes were evaluated using whole genome shotgun metagenomics analyses of fecal DNA collected prior to and after antibiotic treatment. ERT caused significant changes to the gut microbiome that were mitigated in the presence of SYN-006. In addition, SYN-006 attenuated emergence of antibiotic resistance, including encoded beta-lactamases and genes conferring resistance to a broad range of antibiotics such as aminoglycosides and macrolides. SYN-006 has the potential to become the first therapy designed to protect the gut microbiome from all classes of beta-lactam antibiotics and reduce emergence of carbapenem-resistant pathogens.

@article{
 title = {Low dose oral beta-lactamase protects the gut microbiome from oral beta-lactam-mediated damage in dogs},
 type = {article},
 year = {2019},
 keywords = {antibiotic,beta-lactam,beta-lactamase,gut microbiome},
 pages = {477-487},
 volume = {6},
 publisher = {American Institute of Mathematical Sciences},
 id = {3041eb9a-9a1d-3f09-8aaa-cac8c05f3149},
 created = {2025-10-30T12:26:00.974Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.974Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Antibiotics, while lifesaving, damage the gut microbiome and can precipitate proliferation of pathobionts. A strategy to preserve gut microbiome integrity is to eliminate biologically active antimicrobials excreted into the gastrointestinal tract (GI) without negatively affecting antibiotic therapeutic efficacy. Clinical proof of concept was achieved with SYN-004 (ribaxamase), a beta-lactamase enzyme formulated for oral delivery with intravenous penicillins and cephalosporins. Ribaxamase inactivated intestinal ceftriaxone, protected the gut microbiome, and significantly reduced the incidence of Clostridioides difficile disease. For use with oral beta-lactam antibiotics, a delayed release formulation of ribaxamase, SYN-007, was engineered for dissolution in the lower small intestine distal to the site of oral antibiotic absorption. In dogs that received oral amoxicillin, SYN-007 reduced microbiome disruption without interfering with amoxicillin systemic absorption. Here, a study to determine the lowest effective dose of SYN-007 was performed. Dogs received amoxicillin (40 mg/kg, PO, TID) +/– SYN-007 (PO, TID) at three doses, 10 mg, 3 mg, or 1 mg for five days. Serum amoxicillin levels, measured after the first and last antibiotic doses, were not significantly different +/–SYN-007 at all dose levels indicating that SYN-007 did not interfere with amoxicillin systemic absorption. Microbiome analyses demonstrated that amoxicillin significantly reduced bacteria richness and microbiome diversity resulting in altered microbiome composition. However, with all doses of SYN-007, microbiome richness and diversity were not significantly different from pretreatment and changes in microbiome composition were attenuated. These data demonstrate that effective SYN-007 doses can be reduced at least 10-fold while maintaining gut microbiome preservation. The potential to employ low SYN-007 doses to protect the gut microbiota has important implications for enhancing therapeutic outcomes for patients receiving oral beta-lactam antibiotics while simultaneously reducing cost per dose and ultimately, healthcare expenses.},
 bibtype = {article},
 author = {Connelly, Sheila and Fanelli, Brian and Hasan, Nur A. and Colwell, Rita R. and Kaleko, Michael},
 doi = {10.3934/PUBLICHEALTH.2019.4.477},
 journal = {AIMS Public Health},
 number = {4}
}

Antibiotics, while lifesaving, damage the gut microbiome and can precipitate proliferation of pathobionts. A strategy to preserve gut microbiome integrity is to eliminate biologically active antimicrobials excreted into the gastrointestinal tract (GI) without negatively affecting antibiotic therapeutic efficacy. Clinical proof of concept was achieved with SYN-004 (ribaxamase), a beta-lactamase enzyme formulated for oral delivery with intravenous penicillins and cephalosporins. Ribaxamase inactivated intestinal ceftriaxone, protected the gut microbiome, and significantly reduced the incidence of Clostridioides difficile disease. For use with oral beta-lactam antibiotics, a delayed release formulation of ribaxamase, SYN-007, was engineered for dissolution in the lower small intestine distal to the site of oral antibiotic absorption. In dogs that received oral amoxicillin, SYN-007 reduced microbiome disruption without interfering with amoxicillin systemic absorption. Here, a study to determine the lowest effective dose of SYN-007 was performed. Dogs received amoxicillin (40 mg/kg, PO, TID) +/– SYN-007 (PO, TID) at three doses, 10 mg, 3 mg, or 1 mg for five days. Serum amoxicillin levels, measured after the first and last antibiotic doses, were not significantly different +/–SYN-007 at all dose levels indicating that SYN-007 did not interfere with amoxicillin systemic absorption. Microbiome analyses demonstrated that amoxicillin significantly reduced bacteria richness and microbiome diversity resulting in altered microbiome composition. However, with all doses of SYN-007, microbiome richness and diversity were not significantly different from pretreatment and changes in microbiome composition were attenuated. These data demonstrate that effective SYN-007 doses can be reduced at least 10-fold while maintaining gut microbiome preservation. The potential to employ low SYN-007 doses to protect the gut microbiota has important implications for enhancing therapeutic outcomes for patients receiving oral beta-lactam antibiotics while simultaneously reducing cost per dose and ultimately, healthcare expenses.

@article{
 title = {Oral beta-lactamase protects the canine gut microbiome from oral amoxicillin-mediated damage},
 type = {article},
 year = {2019},
 keywords = {Antibiotic resistance,Beta-lactamase,Gut microbiome},
 volume = {7},
 month = {5},
 publisher = {MDPI AG},
 day = {1},
 id = {ada111c7-a95d-3914-9653-208b66d25012},
 created = {2025-10-30T12:26:00.976Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:05.230Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Antibiotics damage the gut microbiome, which can result in overgrowth of pathogenic microorganisms and emergence of antibiotic resistance. Inactivation of antibiotics in the small intestine represents a novel strategy to protect the colonic microbiota. SYN-004 (ribaxamase) is a beta-lactamase formulated for oral delivery intended to degrade intravenously administered beta-lactam antibiotics in the gastrointestinal (GI) tract. The enteric coating of ribaxamase protects the enzyme from stomach acid and mediates pH-dependent release in the upper small intestine, the site of antibiotic biliary excretion. Clinical benefit was established in animal and human studies in which ribaxamase was shown to degrade ceftriaxone in the GI tract, thereby preserving the gut microbiome, significantly reducing Clostridioides difficile disease, and attenuating antibiotic resistance. To expand ribaxamase utility to oral beta-lactams, delayed release formulations of ribaxamase, SYN-007, were engineered to allow enzyme release in the lower small intestine, distal to the site of oral antibiotic absorption. Based on in vitro dissolution profiles, three SYN-007 formulations were selected for evaluation in a canine model of antibiotic-mediated gut dysbiosis. Dogs received amoxicillin (40 mg/kg, PO, TID) +/-SYN-007 (10 mg, PO, TID) for five days. Serum amoxicillin levels were measured after the first and last antibiotic doses and gut microbiomes were evaluated using whole genome shotgun sequence metagenomics analyses of fecal DNA prior to and after antibiotic treatment. Serum amoxicillin levels did not significantly differ +/-SYN-007 after the first dose for all SYN-007 formulations, while only one SYN-007 formulation did not significantly reduce systemic antibiotic concentrations after the last dose. Gut microbiomes of animals receiving amoxicillin alone displayed significant loss of diversity and emergence of antibiotic resistance genes. In contrast, for animals receiving amoxicillin + SYN-007, microbiome diversities were not altered significantly and the presence of antibiotic resistance genes was reduced. These data demonstrate that SYN-007 diminishes amoxicillin-mediated microbiome disruption and mitigates emergence and propagation of antibiotic resistance genes without interfering with antibiotic systemic absorption. Thus, SYN-007 has the potential to protect the gut microbiome by inactivation of beta-lactam antibiotics when administered by both oral and parenteral routes and to reduce emergence of antibiotic-resistant pathogens.},
 bibtype = {article},
 author = {Connelly, Sheila and Fanelli, Brian and Hasan, Nur A. and Colwell, Rita R. and Kaleko, Michael},
 doi = {10.3390/MICROORGANISMS7050150},
 journal = {Microorganisms},
 number = {5}
}

Antibiotics damage the gut microbiome, which can result in overgrowth of pathogenic microorganisms and emergence of antibiotic resistance. Inactivation of antibiotics in the small intestine represents a novel strategy to protect the colonic microbiota. SYN-004 (ribaxamase) is a beta-lactamase formulated for oral delivery intended to degrade intravenously administered beta-lactam antibiotics in the gastrointestinal (GI) tract. The enteric coating of ribaxamase protects the enzyme from stomach acid and mediates pH-dependent release in the upper small intestine, the site of antibiotic biliary excretion. Clinical benefit was established in animal and human studies in which ribaxamase was shown to degrade ceftriaxone in the GI tract, thereby preserving the gut microbiome, significantly reducing Clostridioides difficile disease, and attenuating antibiotic resistance. To expand ribaxamase utility to oral beta-lactams, delayed release formulations of ribaxamase, SYN-007, were engineered to allow enzyme release in the lower small intestine, distal to the site of oral antibiotic absorption. Based on in vitro dissolution profiles, three SYN-007 formulations were selected for evaluation in a canine model of antibiotic-mediated gut dysbiosis. Dogs received amoxicillin (40 mg/kg, PO, TID) +/-SYN-007 (10 mg, PO, TID) for five days. Serum amoxicillin levels were measured after the first and last antibiotic doses and gut microbiomes were evaluated using whole genome shotgun sequence metagenomics analyses of fecal DNA prior to and after antibiotic treatment. Serum amoxicillin levels did not significantly differ +/-SYN-007 after the first dose for all SYN-007 formulations, while only one SYN-007 formulation did not significantly reduce systemic antibiotic concentrations after the last dose. Gut microbiomes of animals receiving amoxicillin alone displayed significant loss of diversity and emergence of antibiotic resistance genes. In contrast, for animals receiving amoxicillin + SYN-007, microbiome diversities were not altered significantly and the presence of antibiotic resistance genes was reduced. These data demonstrate that SYN-007 diminishes amoxicillin-mediated microbiome disruption and mitigates emergence and propagation of antibiotic resistance genes without interfering with antibiotic systemic absorption. Thus, SYN-007 has the potential to protect the gut microbiome by inactivation of beta-lactam antibiotics when administered by both oral and parenteral routes and to reduce emergence of antibiotic-resistant pathogens.

@article{
 title = {Metagenomic profiling of microbial pathogens in the little bighorn river, Montana},
 type = {article},
 year = {2019},
 keywords = {Metagenomics,Pathogen detection,Waterborne disease},
 volume = {16},
 month = {4},
 publisher = {MDPI AG},
 day = {1},
 id = {7513ed24-55c1-307e-b244-56d6f983cb51},
 created = {2025-10-30T12:26:00.980Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:07.311Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The Little Bighorn River is the primary source of water for water treatment plants serving the local Crow Agency population, and has special significance in the spiritual and ceremonial life of the Crow tribe. Unfortunately, the watershed suffers from impaired water quality, with high counts of fecal coliform bacteria routinely measured during run-off events. A metagenomic analysis was carried out to identify potential pathogens in the river water. The Oxford Nanopore MinION platform was used to sequence DNA in near real time to identify both uncultured and a coliform-enriched culture of microbes collected from a popular summer swimming area of the Little Bighorn River. Sequences were analyzed using CosmosID bioinformatics and, in agreement with previous studies, enterohemorrhagic and enteropathogenic Escherichia coli and other E. coli pathotypes were identified. Noteworthy was detection and identification of enteroaggregative E. coli O104:H4 and Vibrio cholerae serotype O1 El Tor, however, cholera toxin genes were not identified. Other pathogenic microbes, as well as virulence genes and antimicrobial resistance markers, were also identified and characterized by metagenomic analyses. It is concluded that metagenomics provides a useful and potentially routine tool for identifying in an in-depth manner microbial contamination of waterways and, thereby, protecting public health.},
 bibtype = {article},
 author = {Hamner, Steve and Brown, Bonnie L. and Hasan, Nur A. and Franklin, Michael J. and Doyle, John and Eggers, Margaret J. and Colwell, Rita R. and Ford, Timothy E.},
 doi = {10.3390/IJERPH16071097},
 journal = {International Journal of Environmental Research and Public Health},
 number = {7}
}

The Little Bighorn River is the primary source of water for water treatment plants serving the local Crow Agency population, and has special significance in the spiritual and ceremonial life of the Crow tribe. Unfortunately, the watershed suffers from impaired water quality, with high counts of fecal coliform bacteria routinely measured during run-off events. A metagenomic analysis was carried out to identify potential pathogens in the river water. The Oxford Nanopore MinION platform was used to sequence DNA in near real time to identify both uncultured and a coliform-enriched culture of microbes collected from a popular summer swimming area of the Little Bighorn River. Sequences were analyzed using CosmosID bioinformatics and, in agreement with previous studies, enterohemorrhagic and enteropathogenic Escherichia coli and other E. coli pathotypes were identified. Noteworthy was detection and identification of enteroaggregative E. coli O104:H4 and Vibrio cholerae serotype O1 El Tor, however, cholera toxin genes were not identified. Other pathogenic microbes, as well as virulence genes and antimicrobial resistance markers, were also identified and characterized by metagenomic analyses. It is concluded that metagenomics provides a useful and potentially routine tool for identifying in an in-depth manner microbial contamination of waterways and, thereby, protecting public health.

@article{
 title = {Drinking Water Microbiome Project: Is it Time?},
 type = {article},
 year = {2019},
 keywords = {drinking water,meta-omics,microbial ecology,microbiome},
 pages = {670-677},
 volume = {27},
 month = {8},
 publisher = {Elsevier Ltd},
 day = {1},
 id = {fd4e4b21-3a80-39d0-9efe-1bf75fc4b598},
 created = {2025-10-30T12:26:00.985Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.985Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Now is an opportune time to foster collaborations across sectors and geographical boundaries to enable development of best practices for drinking water (DW) microbiome research, focusing on accuracy and reproducibility of meta-omic techniques (while learning from past microbiome projects). A large-scale coordinated effort that builds on this foundation will enable the urgently needed comprehensive spatiotemporal understanding and control of DW microbiomes by engineering interventions to protect public health. This opinion paper highlights the need to initiate and conduct a large-scale coordinated DW microbiome project by addressing key knowledge gaps and recommends a roadmap for this effort.},
 bibtype = {article},
 author = {Hull, Natalie M. and Ling, Fangqiong and Pinto, Ameet J. and Albertsen, Mads and Jang, H. Grace and Hong, Pei Ying and Konstantinidis, Konstantinos T. and LeChevallier, Mark and Colwell, Rita R. and Liu, Wen Tso},
 doi = {10.1016/J.TIM.2019.03.011},
 journal = {Trends in Microbiology},
 number = {8}
}

Now is an opportune time to foster collaborations across sectors and geographical boundaries to enable development of best practices for drinking water (DW) microbiome research, focusing on accuracy and reproducibility of meta-omic techniques (while learning from past microbiome projects). A large-scale coordinated effort that builds on this foundation will enable the urgently needed comprehensive spatiotemporal understanding and control of DW microbiomes by engineering interventions to protect public health. This opinion paper highlights the need to initiate and conduct a large-scale coordinated DW microbiome project by addressing key knowledge gaps and recommends a roadmap for this effort.

@article{
 title = {Prosthetic joint infections present diverse and unique microbial communities using combined whole-genome shotgun sequencing and culturing methods},
 type = {article},
 year = {2019},
 keywords = {Microbiology,Microbiome,Polymicrobial,Prosthetic joint infection,Whole-genome sequencing},
 pages = {1507-1516},
 volume = {68},
 publisher = {Microbiology Society},
 id = {734996f8-25dc-31f3-92eb-f9bccd7d7fe6},
 created = {2025-10-30T12:26:00.986Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.986Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction. Prosthetic joint infections (PJIs) are challenging to treat therapeutically because the infectious agents often are resistant to antibiotics and capable of abundant growth in surface-attached biofilms. Though infection rates are low, ca. 1–2%, the overall increase in the sheer number of joint replacement surgeries results in an increase in patients at risk. Aims. This study investigates the consensus of microbial species comprising PJI ecology, which is currently lacking. Methodology. In this study, PJI populations from seven patients were analysed using combined culturing and whole-genome shotgun sequencing (WGSS) to establish population profiles and compare WGSS and culture methods for detection and identification of the PJI microbiome. Results. WGSS detected strains when culture did not, notably dormant, culture-resistant and rare microbes. The CosmosID algorithm was used to predict micro-organisms present in the PJI and discriminate contaminants. However, culturing indicated the presence of microbes falling below the WGSS algorithm threshold. In these instances, microbes cultured are believed to be minor species. The two strategies were combined to build a population profile. Conclusions. Variability between and among PJIs showed that most infections were distinct and unique. Comparative analysis of populations revealed PJIs to form clusters that were related to, but separate from, vaginal, skin and gut microbiomes. Fungi and protists were detected by WGSS, but the role of fungi is just beginning to be understood and for protists it is unknown. These micro-organisms and their novel and strain-specific microbial interactions remain to be determined in current clinical tests.},
 bibtype = {article},
 author = {Weaver, Abigail A. and Hasan, Nur A. and Klaassen, Mark and Karathia, Hiren and Colwell, Rita R. and Shrout, Joshua D.},
 doi = {10.1099/JMM.0.001068},
 journal = {Journal of Medical Microbiology},
 number = {10}
}

Introduction. Prosthetic joint infections (PJIs) are challenging to treat therapeutically because the infectious agents often are resistant to antibiotics and capable of abundant growth in surface-attached biofilms. Though infection rates are low, ca. 1–2%, the overall increase in the sheer number of joint replacement surgeries results in an increase in patients at risk. Aims. This study investigates the consensus of microbial species comprising PJI ecology, which is currently lacking. Methodology. In this study, PJI populations from seven patients were analysed using combined culturing and whole-genome shotgun sequencing (WGSS) to establish population profiles and compare WGSS and culture methods for detection and identification of the PJI microbiome. Results. WGSS detected strains when culture did not, notably dormant, culture-resistant and rare microbes. The CosmosID algorithm was used to predict micro-organisms present in the PJI and discriminate contaminants. However, culturing indicated the presence of microbes falling below the WGSS algorithm threshold. In these instances, microbes cultured are believed to be minor species. The two strategies were combined to build a population profile. Conclusions. Variability between and among PJIs showed that most infections were distinct and unique. Comparative analysis of populations revealed PJIs to form clusters that were related to, but separate from, vaginal, skin and gut microbiomes. Fungi and protists were detected by WGSS, but the role of fungi is just beginning to be understood and for protists it is unknown. These micro-organisms and their novel and strain-specific microbial interactions remain to be determined in current clinical tests.

@article{
 title = {Correction to: Comprehensive benchmarking and ensemble approaches for metagenomic classifiers (Genome Biology (2017) 18 (182) DOI: 10.1186/s13059-017-1299-7)},
 type = {article},
 year = {2019},
 volume = {20},
 month = {4},
 publisher = {BioMed Central Ltd.},
 day = {5},
 id = {1d5500f4-5b10-36b2-807c-9d10cf0877fc},
 created = {2025-10-30T12:26:01.023Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:05.237Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Following publication of the original article [1], the authors would like to highlight the following two corrections. 1) The updated “Availability of data and materials” declaration to the article: The datasets and scripts supporting the conclusions of this article are freely and publicly available through the IMMSA server, ftp://ftpprivate. ncbi.nlm.nih.gov/nist-immsa/IMMSA/ Scripts used for analysis and generating figures are available at: https://scu.med.cornell.edu/git/ abm237/benchmarking_metagenomic_classifiers 2) The authors would like to clarify that the kraken db build command in the manuscript is for the bacterial database; the command for the standard db is available through the kraken manual: krakenbuild -standard -db $DBNAME.},
 bibtype = {article},
 author = {McIntyre, Alexa B.R. and Ounit, Rachid and Afshinnekoo, Ebrahim and Prill, Robert J. and Hénaff, Elizabeth and Alexander, Noah and Minot, Samuel S. and Danko, David and Foox, Jonathan and Ahsanuddin, Sofia and Tighe, Scott and Hasan, Nur A. and Subramanian, Poorani and Moffat, Kelly and Levy, Shawn and Lonardi, Stefano and Greenfield, Nick and Colwell, Rita R. and Rosen, Gail L. and Mason, Christopher E.},
 doi = {10.1186/S13059-019-1687-2},
 journal = {Genome Biology},
 number = {1}
}

Following publication of the original article [1], the authors would like to highlight the following two corrections. 1) The updated “Availability of data and materials” declaration to the article: The datasets and scripts supporting the conclusions of this article are freely and publicly available through the IMMSA server, ftp://ftpprivate. ncbi.nlm.nih.gov/nist-immsa/IMMSA/ Scripts used for analysis and generating figures are available at: https://scu.med.cornell.edu/git/ abm237/benchmarking_metagenomic_classifiers 2) The authors would like to clarify that the kraken db build command in the manuscript is for the bacterial database; the command for the standard db is available through the kraken manual: krakenbuild -standard -db $DBNAME.

@article{
 title = {Metagenome sequencing-based strain-level and functional characterization of supragingival microbiome associated with dental caries in children},
 type = {article},
 year = {2019},
 keywords = {Bacteria,High-throughput nucleotide sequencing,dental caries,metagenome,microbiota},
 volume = {11},
 month = {1},
 publisher = {Taylor and Francis Ltd.},
 day = {1},
 id = {110e585c-697c-3319-9c54-11ae2e40e638},
 created = {2025-10-30T12:26:01.066Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:09.614Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Studies of the microbiome associated with dental caries have largely relied on 16S rRNA sequence analysis, which is associated with PCR biases, low taxonomic resolution, and inability to accurately study functions. Here, we employed whole metagenome shotgun sequencing, coupled with high-resolution analysis algorithm, to analyze supragingival microbiomes from 30 children with or without dental caries. A total of 726 bacterial strains belonging to 406 species, in addition to 34 bacteriophages were identified. A core bacteriome was identified at the species and strain levels. Species of Prevotella, Veillonella, as yet unnamed Actinomyces, and Atopobium showed strongest association with caries; Streptococcus sp. AS14 and Leptotrichia sp. Oral taxon 225, among others, were overabundant in caries-free. For several species, the association was strain-specific. Furthermore, for some species, e.g. Streptococcus mitis and Streptococcus sanguinis, sister strains showed differential associations. Noteworthy, associations were also identified for phages: Streptococcus phage M102 with caries and Haemophilus phage HP1 with caries-free. Functionally, potentially relevant features were identified including urate, vitamin K2, and polyamine biosynthesis in association with caries; and three deiminases and lactate dehydrogenase with health. The results demonstrate new associations between the microbiome and dental caries at the strain and functional levels that need further investigation.},
 bibtype = {article},
 author = {Al-Hebshi, Nezar Noor and Baraniya, Divyashri and Chen, Tsute and Hill, Jennifer and Puri, Sumant and Tellez, Marisol and Hassan, Nur A. and Colwell, Rita R. and Ismail, Amid},
 doi = {10.1080/20002297.2018.1557986},
 journal = {Journal of Oral Microbiology},
 number = {1}
}

Studies of the microbiome associated with dental caries have largely relied on 16S rRNA sequence analysis, which is associated with PCR biases, low taxonomic resolution, and inability to accurately study functions. Here, we employed whole metagenome shotgun sequencing, coupled with high-resolution analysis algorithm, to analyze supragingival microbiomes from 30 children with or without dental caries. A total of 726 bacterial strains belonging to 406 species, in addition to 34 bacteriophages were identified. A core bacteriome was identified at the species and strain levels. Species of Prevotella, Veillonella, as yet unnamed Actinomyces, and Atopobium showed strongest association with caries; Streptococcus sp. AS14 and Leptotrichia sp. Oral taxon 225, among others, were overabundant in caries-free. For several species, the association was strain-specific. Furthermore, for some species, e.g. Streptococcus mitis and Streptococcus sanguinis, sister strains showed differential associations. Noteworthy, associations were also identified for phages: Streptococcus phage M102 with caries and Haemophilus phage HP1 with caries-free. Functionally, potentially relevant features were identified including urate, vitamin K2, and polyamine biosynthesis in association with caries; and three deiminases and lactate dehydrogenase with health. The results demonstrate new associations between the microbiome and dental caries at the strain and functional levels that need further investigation.

@article{
 title = {T6SS and ExoA of flesh-eating Aeromonas hydrophila in peritonitis and necrotizing fasciitis during mono- And polymicrobial infections},
 type = {article},
 year = {2019},
 keywords = {Animal models,ExoA,Mono- and polymicrobial Aeromonas hydrophila infections,Necrotizing fasciitis,T6SS},
 pages = {24084-24092},
 volume = {116},
 month = {11},
 publisher = {National Academy of Sciences},
 day = {26},
 id = {11859d40-fd34-39e3-93be-aedbcf4fcb8f},
 created = {2025-10-30T12:26:01.181Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:10.043Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {An earlier report described a human case of necrotizing fasciitis (NF) caused by mixed infection with 4 Aeromonas hydrophila strains (NF1–NF4). While the NF2, NF3, and NF4 strains were clonal and possessed exotoxin A (ExoA), the NF1 strain was determined to be phylogenetically distinct, harboring a unique type 6 secretion system (T6SS) effector (TseC). During NF1 and NF2 mixed infection, only NF1 disseminated, while NF2 was rapidly killed by a contact-dependent mechanism and macrophage phagocytosis, as was demonstrated by using in vitro models. To confirm these findings, we developed 2 NF1 mutants (NF1ΔtseC and NF1ΔvasK); vasK encodes an essential T6SS structural component. NF1 VasK and TseC were proven to be involved in contact-dependent killing of NF2 in vitro, as well as in its elimination at the intramuscular injection site in vivo during mixed infection, with overall reduced mouse mortality. ExoA was shown to have an important role in NF by both NF1-exoA (with cis exoA) and NF2 during monomicrobial infection. However, the contribution of ExoA was more important for NF2 than NF1 in the murine peritonitis model. The NF2ΔexoA mutant did not significantly alter animal mortality or NF1 dissemination during mixed infection in the NF model, suggesting that the ExoA activity was significant at the injection site. Immunization of mice to ExoA protected animals from NF2 monomicrobial challenge, but not from polymicrobial infection because of NF2 clearance. This study clarified the roles of T6SS and ExoA in pathogenesis caused by A. hydrophila NF strains in both mouse peritonitis and NF models in monomicrobial and polymicrobial infections.},
 bibtype = {article},
 author = {Fernández-Bravo, Ana and Kilgore, Paul B. and Andersson, Jourdan A. and Blears, Elizabeth and Figueras, Maria José and Hasan, Nur A. and Colwell, Rita R. and Sha, Jian and Chopra, Ashok K.},
 doi = {10.1073/PNAS.1914395116},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 number = {48}
}

An earlier report described a human case of necrotizing fasciitis (NF) caused by mixed infection with 4 Aeromonas hydrophila strains (NF1–NF4). While the NF2, NF3, and NF4 strains were clonal and possessed exotoxin A (ExoA), the NF1 strain was determined to be phylogenetically distinct, harboring a unique type 6 secretion system (T6SS) effector (TseC). During NF1 and NF2 mixed infection, only NF1 disseminated, while NF2 was rapidly killed by a contact-dependent mechanism and macrophage phagocytosis, as was demonstrated by using in vitro models. To confirm these findings, we developed 2 NF1 mutants (NF1ΔtseC and NF1ΔvasK); vasK encodes an essential T6SS structural component. NF1 VasK and TseC were proven to be involved in contact-dependent killing of NF2 in vitro, as well as in its elimination at the intramuscular injection site in vivo during mixed infection, with overall reduced mouse mortality. ExoA was shown to have an important role in NF by both NF1-exoA (with cis exoA) and NF2 during monomicrobial infection. However, the contribution of ExoA was more important for NF2 than NF1 in the murine peritonitis model. The NF2ΔexoA mutant did not significantly alter animal mortality or NF1 dissemination during mixed infection in the NF model, suggesting that the ExoA activity was significant at the injection site. Immunization of mice to ExoA protected animals from NF2 monomicrobial challenge, but not from polymicrobial infection because of NF2 clearance. This study clarified the roles of T6SS and ExoA in pathogenesis caused by A. hydrophila NF strains in both mouse peritonitis and NF models in monomicrobial and polymicrobial infections.

@article{
 title = {Olive oil quality classification and measurement of its organoleptic attributes by untargeted GC–MS and multivariate statistical-based approach},
 type = {article},
 year = {2019},
 keywords = {Dynamic headspace,Foodomics,GC–MS,Olive oil,PARAFAC2},
 pages = {488-496},
 volume = {271},
 month = {1},
 publisher = {Elsevier Ltd},
 day = {15},
 id = {cd15eee8-638a-33e8-9b7d-5936edd55702},
 created = {2025-10-30T12:28:33.482Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:33.482Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The capabilities of dynamic headspace entrainment followed by thermal desorption in combination with gas chromatography (GC) coupled to single quadrupole mass spectrometry (MS) have been tested for the determination of volatile components of olive oil. This technique has shown a great potential for olive oil quality classification by using an untargeted approach. The data processing strategy consisted of three different steps: component detection from GC–MS data using novel data treatment software PARADISe, a multivariate analysis using EZ-Info, and the creation of the statistical models. The great number of compounds determined enabled not only the development of a quality classification method as a complementary tool to the official established method “PANEL TEST” but also a correlation between these compounds and different types of defect. Classification method was finally validated using blind samples. An accuracy of 85% in oil classification was obtained, with 100% of extra virgin samples correctly classified.},
 bibtype = {article},
 author = {Sales, C. and Portolés, T. and Johnsen, L. G. and Danielsen, M. and Beltran, J.},
 doi = {10.1016/j.foodchem.2018.07.200},
 journal = {Food Chemistry}
}

The capabilities of dynamic headspace entrainment followed by thermal desorption in combination with gas chromatography (GC) coupled to single quadrupole mass spectrometry (MS) have been tested for the determination of volatile components of olive oil. This technique has shown a great potential for olive oil quality classification by using an untargeted approach. The data processing strategy consisted of three different steps: component detection from GC–MS data using novel data treatment software PARADISe, a multivariate analysis using EZ-Info, and the creation of the statistical models. The great number of compounds determined enabled not only the development of a quality classification method as a complementary tool to the official established method “PANEL TEST” but also a correlation between these compounds and different types of defect. Classification method was finally validated using blind samples. An accuracy of 85% in oil classification was obtained, with 100% of extra virgin samples correctly classified.

@article{
 title = {Antibiotic treatment of rat dams affects bacterial colonization and causes decreased weight gain in pups},
 type = {article},
 year = {2018},
 keywords = {Henrik Munch Roager,MEDLINE,Martin Iain Bahl,Monica Vera-Lise Tulstrup,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,PMC6137057,PubMed Abstract,doi:10.1038/s42003-018-0140-5,pmid:30272021},
 volume = {1},
 websites = {https://pubmed.ncbi.nlm.nih.gov/30272021/},
 month = {12},
 publisher = {Commun Biol},
 day = {1},
 id = {c3d43ee6-af53-3a5a-813a-b1349a99f8fa},
 created = {2025-07-07T13:25:15.876Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:03.133Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Intergenerational transmission of bacteria during birth initiates the natural successional development of the intestinal microbiota in mammals. This process can be disrupted by antibiotic exposure, potentially affecting early-life microbiota-dependent metabolic programming. In the present study, we specifically investigate the metabolic consequences of exposing neonate Wistar rats to an antibiotic-perturbed low-diversity microbiota from birth until weaning, without exposing the pups directly to antibiotics. Here, we show that pups born from both amoxicillin and vancomycin-treated dams gain less weight than controls. This was concordant with lower feed intake as well as increased colonic expression of the PYY satiety hormone gene at weaning. The weight difference persists into adulthood even though the initial differences in gut microbiota subsided. Our results demonstrate that early-life exposure to an antibiotic-perturbed low-diversity microbiota is sufficient to cause changes in body weight persisting into adulthood.},
 bibtype = {article},
 author = {Tulstrup, Monica Vera Lise and Roager, Henrik Munch and Thaarup, Ida Clement and Frandsen, Henrik Lauritz and Frøkiær, Hanne and Licht, Tine Rask and Bahl, Martin Iain},
 doi = {10.1038/S42003-018-0140-5},
 journal = {Communications biology},
 number = {1}
}

Intergenerational transmission of bacteria during birth initiates the natural successional development of the intestinal microbiota in mammals. This process can be disrupted by antibiotic exposure, potentially affecting early-life microbiota-dependent metabolic programming. In the present study, we specifically investigate the metabolic consequences of exposing neonate Wistar rats to an antibiotic-perturbed low-diversity microbiota from birth until weaning, without exposing the pups directly to antibiotics. Here, we show that pups born from both amoxicillin and vancomycin-treated dams gain less weight than controls. This was concordant with lower feed intake as well as increased colonic expression of the PYY satiety hormone gene at weaning. The weight difference persists into adulthood even though the initial differences in gut microbiota subsided. Our results demonstrate that early-life exposure to an antibiotic-perturbed low-diversity microbiota is sufficient to cause changes in body weight persisting into adulthood.

@article{
 title = {Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation},
 type = {article},
 year = {2018},
 pages = {1321-1335.e20},
 volume = {175},
 websites = {http://www.cell.com/article/S0092867418313230/fulltext,http://www.cell.com/article/S0092867418313230/abstract,https://www.cell.com/cell/abstract/S0092-8674(18)31323-0},
 month = {11},
 publisher = {Cell Press},
 day = {15},
 id = {f59eb44c-2474-3aed-9944-72139f25069e},
 created = {2025-07-07T13:25:16.259Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:03.463Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Adaptation of liver to the postprandial state requires coordinated regulation of protein synthesis and folding aligned with changes in lipid metabolism. Here we demonstrate that sensory food perception is sufficient to elicit early activation of hepatic mTOR signaling, Xbp1 splicing, increased expression of ER-stress genes, and phosphatidylcholine synthesis, which translate into a rapid morphological ER remodeling. These responses overlap with those activated during refeeding, where they are maintained and constantly increased upon nutrient supply. Sensory food perception activates POMC neurons in the hypothalamus, optogenetic activation of POMC neurons activates hepatic mTOR signaling and Xbp1 splicing, whereas lack of MC4R expression attenuates these responses to sensory food perception. Chemogenetic POMC-neuron activation promotes sympathetic nerve activity (SNA) subserving the liver, and norepinephrine evokes the same responses in hepatocytes in vitro and in liver in vivo as observed upon sensory food perception. Collectively, our experiments unravel that sensory food perception coordinately primes postprandial liver ER adaption through a melanocortin-SNA-mTOR-Xbp1s axis. Video Abstract: The sight and smell of food are sufficient to induce liver endoplasmic reticulum reprogramming through a hypothalamic circuit, thereby anticipating the metabolic changes required for nutrient intake.},
 bibtype = {article},
 author = {Brandt, Claus and Nolte, Hendrik and Henschke, Sinika and Engström Ruud, Linda and Awazawa, Motoharu and Morgan, Donald A. and Gabel, Paula and Sprenger, Hans Georg and Hess, Martin E. and Günther, Stefan and Langer, Thomas and Rahmouni, Kamal and Fenselau, Henning and Krüger, Marcus and Brüning, Jens C.},
 doi = {10.1016/J.CELL.2018.10.015/ATTACHMENT/248FD5C3-E306-4966-AB5E-D7E6DB91C76B/MMC5.XLSX},
 journal = {Cell},
 number = {5}
}

Adaptation of liver to the postprandial state requires coordinated regulation of protein synthesis and folding aligned with changes in lipid metabolism. Here we demonstrate that sensory food perception is sufficient to elicit early activation of hepatic mTOR signaling, Xbp1 splicing, increased expression of ER-stress genes, and phosphatidylcholine synthesis, which translate into a rapid morphological ER remodeling. These responses overlap with those activated during refeeding, where they are maintained and constantly increased upon nutrient supply. Sensory food perception activates POMC neurons in the hypothalamus, optogenetic activation of POMC neurons activates hepatic mTOR signaling and Xbp1 splicing, whereas lack of MC4R expression attenuates these responses to sensory food perception. Chemogenetic POMC-neuron activation promotes sympathetic nerve activity (SNA) subserving the liver, and norepinephrine evokes the same responses in hepatocytes in vitro and in liver in vivo as observed upon sensory food perception. Collectively, our experiments unravel that sensory food perception coordinately primes postprandial liver ER adaption through a melanocortin-SNA-mTOR-Xbp1s axis. Video Abstract: The sight and smell of food are sufficient to induce liver endoplasmic reticulum reprogramming through a hypothalamic circuit, thereby anticipating the metabolic changes required for nutrient intake.

@article{
 title = {Glyphosate has limited short-term effects on commensal bacterial community composition in the gut environment due to sufficient aromatic amino acid levels},
 type = {article},
 year = {2018},
 keywords = {Aromatic amino acid,Glyfonova®,Glyphosate,Gut,Intestinal,MIC,Microbiota,Roundup®},
 pages = {364-376},
 volume = {233},
 month = {2},
 publisher = {Elsevier},
 day = {1},
 id = {4b7dbb1a-24df-3a57-87bc-6e7b483bac05},
 created = {2025-07-07T13:25:16.598Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:03.797Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Recently, concerns have been raised that residues of glyphosate-based herbicides may interfere with the homeostasis of the intestinal bacterial community and thereby affect the health of humans or animals. The biochemical pathway for aromatic amino acid synthesis (Shikimate pathway), which is specifically inhibited by glyphosate, is shared by plants and numerous bacterial species. Several in vitro studies have shown that various groups of intestinal bacteria may be differently affected by glyphosate. Here, we present results from an animal exposure trial combining deep 16S rRNA gene sequencing of the bacterial community with liquid chromatography mass spectrometry (LC-MS) based metabolic profiling of aromatic amino acids and their downstream metabolites. We found that glyphosate as well as the commercial formulation Glyfonova®450 PLUS administered at up to fifty times the established European Acceptable Daily Intake (ADI = 0.5 mg/kg body weight) had very limited effects on bacterial community composition in Sprague Dawley rats during a two-week exposure trial. The effect of glyphosate on prototrophic bacterial growth was highly dependent on the availability of aromatic amino acids, suggesting that the observed limited effect on bacterial composition was due to the presence of sufficient amounts of aromatic amino acids in the intestinal environment. A strong correlation was observed between intestinal concentrations of glyphosate and intestinal pH, which may partly be explained by an observed reduction in acetic acid produced by the gut bacteria. We conclude that sufficient intestinal levels of aromatic amino acids provided by the diet alleviates the need for bacterial synthesis of aromatic amino acids and thus prevents an antimicrobial effect of glyphosate in vivo. It is however possible that the situation is different in cases of human malnutrition or in production animals. Oral exposure to glyphosate in rats at fifty times the acceptable daily intake for humans has negligible effects on the gut microbiota composition due to sufficient in situ aromatic amino acid levels.},
 bibtype = {article},
 author = {Nielsen, Lene Nørby and Roager, Henrik M. and Casas, Mònica Escolà and Frandsen, Henrik L. and Gosewinkel, Ulrich and Bester, Kai and Licht, Tine Rask and Hendriksen, Niels Bohse and Bahl, Martin Iain},
 doi = {10.1016/J.ENVPOL.2017.10.016},
 journal = {Environmental Pollution}
}

Recently, concerns have been raised that residues of glyphosate-based herbicides may interfere with the homeostasis of the intestinal bacterial community and thereby affect the health of humans or animals. The biochemical pathway for aromatic amino acid synthesis (Shikimate pathway), which is specifically inhibited by glyphosate, is shared by plants and numerous bacterial species. Several in vitro studies have shown that various groups of intestinal bacteria may be differently affected by glyphosate. Here, we present results from an animal exposure trial combining deep 16S rRNA gene sequencing of the bacterial community with liquid chromatography mass spectrometry (LC-MS) based metabolic profiling of aromatic amino acids and their downstream metabolites. We found that glyphosate as well as the commercial formulation Glyfonova®450 PLUS administered at up to fifty times the established European Acceptable Daily Intake (ADI = 0.5 mg/kg body weight) had very limited effects on bacterial community composition in Sprague Dawley rats during a two-week exposure trial. The effect of glyphosate on prototrophic bacterial growth was highly dependent on the availability of aromatic amino acids, suggesting that the observed limited effect on bacterial composition was due to the presence of sufficient amounts of aromatic amino acids in the intestinal environment. A strong correlation was observed between intestinal concentrations of glyphosate and intestinal pH, which may partly be explained by an observed reduction in acetic acid produced by the gut bacteria. We conclude that sufficient intestinal levels of aromatic amino acids provided by the diet alleviates the need for bacterial synthesis of aromatic amino acids and thus prevents an antimicrobial effect of glyphosate in vivo. It is however possible that the situation is different in cases of human malnutrition or in production animals. Oral exposure to glyphosate in rats at fifty times the acceptable daily intake for humans has negligible effects on the gut microbiota composition due to sufficient in situ aromatic amino acid levels.

@article{
 title = {Human gut bacteria as potent class I histone deacetylase inhibitors in vitro through production of butyric acid and valeric acid},
 type = {article},
 year = {2018},
 keywords = {Butyric acids,Colorectal cancer,Consortia,Epigenetics,Gut bacteria,Histones,Metabolites,Protein extraction},
 pages = {e0201073},
 volume = {13},
 websites = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201073},
 month = {7},
 publisher = {Public Library of Science},
 day = {1},
 id = {20318f3c-2fc0-31d2-9d80-19f13855da53},
 created = {2025-07-07T13:25:17.073Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:04.149Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Overexpression of histone deacetylase (HDAC) isoforms has been implicated in a variety of disease pathologies, from cancer and colitis to cardiovascular disease and neurodegeneration, thus HDAC inhibitors have a long history as therapeutic targets. The gut microbiota can influence HDAC activity via microbial-derived metabolites. While HDAC inhibition (HDI) by gut commensals has long been attributed to the short chain fatty acid (SCFA) butyrate, the potent metabolic reservoir provided by the gut microbiota and its role in host physiology warrants further investigation in a variety of diseases. Cell-free supernatants (CFS) of 79 phylogenetically diverse gut commensals isolated from healthy human donors were screened for their SCFA profile and their total HDAC inhibitory properties. The three most potent HDAC inhibiting strains were further evaluated and subjected to additional analysis of specific class I and class II HDAC inhibition. All three HDAC inhibitors are butyrate producing strains, and one of these also produced substantial levels of valeric acid and hexanoic acid. Valeric acid was identified as a potential contributor to the HDAC inhibitory effects. This bacterial strain, Megasphaera massiliensis MRx0029, was added to a model microbial consortium to assess its metabolic activity in interaction with a complex community. M. massiliensis MRx0029 successfully established in the consortium and enhanced the total and specific HDAC inhibitory function by increasing the capacity of the community to produce butyrate and valeric acid. We here show that single bacterial strains from the human gut microbiota have potential as novel HDI therapeutics for disease areas involving host epigenetic aberrations.},
 bibtype = {article},
 author = {Yuille, Samantha and Reichardt, Nicole and Panda, Suchita and Dunbar, Hayley and Mulder, Imke E.},
 doi = {10.1371/JOURNAL.PONE.0201073},
 journal = {PLOS ONE},
 number = {7}
}

Overexpression of histone deacetylase (HDAC) isoforms has been implicated in a variety of disease pathologies, from cancer and colitis to cardiovascular disease and neurodegeneration, thus HDAC inhibitors have a long history as therapeutic targets. The gut microbiota can influence HDAC activity via microbial-derived metabolites. While HDAC inhibition (HDI) by gut commensals has long been attributed to the short chain fatty acid (SCFA) butyrate, the potent metabolic reservoir provided by the gut microbiota and its role in host physiology warrants further investigation in a variety of diseases. Cell-free supernatants (CFS) of 79 phylogenetically diverse gut commensals isolated from healthy human donors were screened for their SCFA profile and their total HDAC inhibitory properties. The three most potent HDAC inhibiting strains were further evaluated and subjected to additional analysis of specific class I and class II HDAC inhibition. All three HDAC inhibitors are butyrate producing strains, and one of these also produced substantial levels of valeric acid and hexanoic acid. Valeric acid was identified as a potential contributor to the HDAC inhibitory effects. This bacterial strain, Megasphaera massiliensis MRx0029, was added to a model microbial consortium to assess its metabolic activity in interaction with a complex community. M. massiliensis MRx0029 successfully established in the consortium and enhanced the total and specific HDAC inhibitory function by increasing the capacity of the community to produce butyrate and valeric acid. We here show that single bacterial strains from the human gut microbiota have potential as novel HDI therapeutics for disease areas involving host epigenetic aberrations.

@article{
 title = {Influence of gemcitabine chemotherapy on the microbiota of pancreatic cancer xenografted mice},
 type = {article},
 year = {2018},
 keywords = {Gemcitabine,Inflammation,Microbiota,Pancreatic cancer},
 pages = {773-782},
 volume = {81},
 websites = {https://link.springer.com/article/10.1007/s00280-018-3549-0},
 month = {4},
 publisher = {Springer Verlag},
 day = {1},
 id = {6b925428-a01c-30fa-9ad3-478e2e0ed463},
 created = {2025-07-07T13:25:17.426Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:17.426Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background and aims: Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of cancer-related death. We aimed to evaluate whether gemcitabine treatment shapes the gut microbiota in a model of PDAC xenografted mice. Materials and methods: Pancreatic cancer xenograft mice were subjected to gemcitabine injection once per week for 3 weeks to assess the tumor volume as compared to control mice injected with normal saline solution. The composition of fecal microbiota, the activation of NF-kB pathway in cancer tissues and the serum metabolomics were further analyzed. Results: Gemcitabine considerably decreases the proportion of Gram- positive Firmicutes (from about 39 to 17%) and the Gram- negative Bacteroidetes (from 38 to 17%) which are the two dominant phyla in the gut of tumor-bearing control mice. This downshift was replaced by an increase of Proteobacteria (Escherichia coli and Aeromonas hydrophila) from 15 up to 32% and Verrucomicrobia (Akkermansia muciniphila) from 5 to 33% in the gut of drug-receiving mice. An overall increase in inflammation-associated bacteria was observed upon gemcitabine. Consistently, activation of the NF-kB canonical pathway was found in cancer tissues from gemcitabine-treated mice. Serum metabolomics revealed a significant decrease of the purine compounds inosine and xanthine, and a decreasing trend for their metabolically-related molecule hypoxanthine. Discussion: Understanding chemotherapy side effects may explain the lack of activity or the chemoresistant processes and it may help to set up strategies to improve the effectiveness of therapy.},
 bibtype = {article},
 author = {Panebianco, Concetta and Adamberg, Kaarel and Jaagura, Madis and Copetti, Massimiliano and Fontana, Andrea and Adamberg, Signe and Kolk, Kaia and Vilu, Raivo and Andriulli, Angelo and Pazienza, Valerio},
 doi = {10.1007/S00280-018-3549-0/METRICS},
 journal = {Cancer Chemotherapy and Pharmacology},
 number = {4}
}

Background and aims: Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of cancer-related death. We aimed to evaluate whether gemcitabine treatment shapes the gut microbiota in a model of PDAC xenografted mice. Materials and methods: Pancreatic cancer xenograft mice were subjected to gemcitabine injection once per week for 3 weeks to assess the tumor volume as compared to control mice injected with normal saline solution. The composition of fecal microbiota, the activation of NF-kB pathway in cancer tissues and the serum metabolomics were further analyzed. Results: Gemcitabine considerably decreases the proportion of Gram- positive Firmicutes (from about 39 to 17%) and the Gram- negative Bacteroidetes (from 38 to 17%) which are the two dominant phyla in the gut of tumor-bearing control mice. This downshift was replaced by an increase of Proteobacteria (Escherichia coli and Aeromonas hydrophila) from 15 up to 32% and Verrucomicrobia (Akkermansia muciniphila) from 5 to 33% in the gut of drug-receiving mice. An overall increase in inflammation-associated bacteria was observed upon gemcitabine. Consistently, activation of the NF-kB canonical pathway was found in cancer tissues from gemcitabine-treated mice. Serum metabolomics revealed a significant decrease of the purine compounds inosine and xanthine, and a decreasing trend for their metabolically-related molecule hypoxanthine. Discussion: Understanding chemotherapy side effects may explain the lack of activity or the chemoresistant processes and it may help to set up strategies to improve the effectiveness of therapy.

@phdthesis{
 title = {Streptococcus pneumoniae - stress hormone interactions},
 type = {phdthesis},
 year = {2018},
 keywords = {IR content},
 websites = {/articles/thesis/Streptococcus_pneumoniae_-_stress_hormone_interactions/10216121/1},
 month = {2},
 publisher = {University of Leicester},
 day = {26},
 id = {9ecc4cf4-9a3b-37f5-9aeb-0979add99edf},
 created = {2025-07-07T13:25:17.744Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:04.574Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Streptococcus pneumoniae is one of the most important bacterial pathogens of humans causing a wide range of mild to life-threating diseases. It is also a commensal microorganism in the nasopharynx of up to 60% of people. Fundamental aspects of its ability for transition from colonisation to an infectious state as well as how bacterial-host interactions influence this process are largely unknown. In the field of microbial endocrinology, it has been well established in mainly Gram-negative bacteria that stress hormones such as norepinephrine epinephrine and dopamine play an essential role in determining the outcome of bacterial infections. This study successfully established the conditions to investigate S. pneumoniae-stress hormone interactions using modified serum-SAPI media. 13 mutants lacking two-component regulatory system and 4 two-component system fusion reporter strains were created, and examined for their role in S. pneumoniae-stress hormone interactions. This study demonstrated that S. pneumoniae is stress hormone responsive and has mechanisms to recognise and process host stress hormones by a transferrin-iron delivery mechanism, which evidence suggests might be mediated via the TCS09 system since hormone-induced growth and radiolabelled norepinephrine and Fe uptake were reduced in a ΔTCS09 mutant. In addition, the pneumococcal response to stress hormone exposure resulted in a change in cell-cell association from chains into diplococci and cell morphology by reducing cell size and the capsule. Furthermore, the pneumococcal exposure to norepinephrine also increased biofilm formation and significantly altered metabolism. The analysis of in vivo experiments indicated that a stress hormone encounter might trigger translocation from the nasopharynx into the lungs, which may enhance S. pneumoniae in its transition from commensal to pathogen. Therefore, the pneumococcal ability to respond to host stress signals may be key to its capacity to cause life-threatening pneumonia, septicaemia and meningitis.},
 bibtype = {phdthesis},
 author = {Fayez Abdullah Alghofaili, by and Abdullah Alghofaili, Fayez}
}

Streptococcus pneumoniae is one of the most important bacterial pathogens of humans causing a wide range of mild to life-threating diseases. It is also a commensal microorganism in the nasopharynx of up to 60% of people. Fundamental aspects of its ability for transition from colonisation to an infectious state as well as how bacterial-host interactions influence this process are largely unknown. In the field of microbial endocrinology, it has been well established in mainly Gram-negative bacteria that stress hormones such as norepinephrine epinephrine and dopamine play an essential role in determining the outcome of bacterial infections. This study successfully established the conditions to investigate S. pneumoniae-stress hormone interactions using modified serum-SAPI media. 13 mutants lacking two-component regulatory system and 4 two-component system fusion reporter strains were created, and examined for their role in S. pneumoniae-stress hormone interactions. This study demonstrated that S. pneumoniae is stress hormone responsive and has mechanisms to recognise and process host stress hormones by a transferrin-iron delivery mechanism, which evidence suggests might be mediated via the TCS09 system since hormone-induced growth and radiolabelled norepinephrine and Fe uptake were reduced in a ΔTCS09 mutant. In addition, the pneumococcal response to stress hormone exposure resulted in a change in cell-cell association from chains into diplococci and cell morphology by reducing cell size and the capsule. Furthermore, the pneumococcal exposure to norepinephrine also increased biofilm formation and significantly altered metabolism. The analysis of in vivo experiments indicated that a stress hormone encounter might trigger translocation from the nasopharynx into the lungs, which may enhance S. pneumoniae in its transition from commensal to pathogen. Therefore, the pneumococcal ability to respond to host stress signals may be key to its capacity to cause life-threatening pneumonia, septicaemia and meningitis.

@article{
 title = {A computational framework to integrate high-throughput ‘-omics’ datasets for the identification of potential mechanistic links},
 type = {article},
 year = {2018},
 pages = {2781-2800},
 volume = {13},
 id = {ad38f124-ffb8-3745-96aa-d4bf99743c4a},
 created = {2025-07-07T13:25:18.061Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:04.930Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Pedersen2018},
 private_publication = {false},
 abstract = {We recently presented a three-pronged association study that integrated human intestinal microbiome data derived from shotgun-based sequencing with untargeted serum metabolome data and measures of host physiology. Metabolome and microbiome data are high dimensional, posing a major challenge for data integration. Here, we present a step-by-step computational protocol that details and discusses the dimensionality-reduction techniques used and methods for subsequent integration and interpretation of such heterogeneous types of data. Dimensionality reduction was achieved through a combination of data normalization approaches, binning of co-abundant genes and metabolites, and integration of prior biological knowledge. The use of prior knowledge to overcome functional redundancy across microbiome species is one central advance of our method over available alternative approaches. Applying this framework, other investigators can integrate various ‘-omics’ readouts with variables of host physiology or any other phenotype of interest (e.g., connecting host and microbiome readouts to disease severity or treatment outcome in a clinical cohort) in a three-pronged association analysis to identify potential mechanistic links to be tested in experimental settings. Although we originally developed the framework for a human metabolome–microbiome study, it is generalizable to other organisms and environmental metagenomes, as well as to studies including other -omics domains such as transcriptomics and proteomics. The provided R code runs in ~1 h on a standard PC.},
 bibtype = {article},
 author = {Pedersen, Helle Krogh and Forslund, Sofia K. and Gudmundsdottir, Valborg and Petersen, Anders Østergaard and Hildebrand, Falk and Hyötyläinen, Tuulia and Nielsen, Trine and Hansen, Torben and Bork, Peer and Ehrlich, S. Dusko and Brunak, Søren and Oresic, Matej and Pedersen, Oluf and Nielsen, Henrik Bjørn},
 doi = {10.1038/s41596-018-0064-z},
 journal = {Nature Protocols},
 number = {12}
}

We recently presented a three-pronged association study that integrated human intestinal microbiome data derived from shotgun-based sequencing with untargeted serum metabolome data and measures of host physiology. Metabolome and microbiome data are high dimensional, posing a major challenge for data integration. Here, we present a step-by-step computational protocol that details and discusses the dimensionality-reduction techniques used and methods for subsequent integration and interpretation of such heterogeneous types of data. Dimensionality reduction was achieved through a combination of data normalization approaches, binning of co-abundant genes and metabolites, and integration of prior biological knowledge. The use of prior knowledge to overcome functional redundancy across microbiome species is one central advance of our method over available alternative approaches. Applying this framework, other investigators can integrate various ‘-omics’ readouts with variables of host physiology or any other phenotype of interest (e.g., connecting host and microbiome readouts to disease severity or treatment outcome in a clinical cohort) in a three-pronged association analysis to identify potential mechanistic links to be tested in experimental settings. Although we originally developed the framework for a human metabolome–microbiome study, it is generalizable to other organisms and environmental metagenomes, as well as to studies including other -omics domains such as transcriptomics and proteomics. The provided R code runs in ~1 h on a standard PC.

@article{
 title = {A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults},
 type = {article},
 year = {2018},
 volume = {9},
 id = {b1dcf237-e3d3-3597-8510-823ea724f3ba},
 created = {2025-07-07T13:25:18.559Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:05.269Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Hansen2018},
 private_publication = {false},
 abstract = {Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.},
 bibtype = {article},
 author = {Hansen, Lea B.S. and Roager, Henrik M. and Søndertoft, Nadja B. and Gøbel, Rikke J. and Kristensen, Mette and Vallès-Colomer, Mireia and Vieira-Silva, Sara and Ibrügger, Sabine and Lind, Mads V. and Mærkedahl, Rasmus B. and Bahl, Martin I. and Madsen, Mia L. and Havelund, Jesper and Falony, Gwen and Tetens, Inge and Nielsen, Trine and Allin, Kristine H. and Frandsen, Henrik L. and Hartmann, Bolette and Holst, Jens Juul and Sparholt, Morten H. and Holck, Jesper and Blennow, Andreas and Moll, Janne Marie and Meyer, Anne S. and Hoppe, Camilla and Poulsen, Jørgen H. and Carvalho, Vera and Sagnelli, Domenico and Dalgaard, Marlene D. and Christensen, Anders F. and Lydolph, Magnus Christian and Ross, Alastair B. and Villas-Bôas, Silas and Brix, Susanne and Sicheritz-Pontén, Thomas and Buschard, Karsten and Linneberg, Allan and Rumessen, Jüri J. and Ekstrøm, Claus T. and Ritz, Christian and Kristiansen, Karsten and Nielsen, H. Bjørn and Vestergaard, Henrik and Færgeman, Nils J. and Raes, Jeroen and Frøkiær, Hanne and Hansen, Torben and Lauritzen, Lotte and Gupta, Ramneek and Licht, Tine Rask and Pedersen, Oluf},
 doi = {10.1038/s41467-018-07019-x},
 journal = {Nature Communications},
 number = {1}
}

Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.

@article{
 title = {Mechanisms Preserving Insulin Action during High Dietary Fat Intake},
 type = {article},
 year = {2018},
 pages = {1-14},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S1550413118305655},
 publisher = {Elsevier Inc.},
 id = {2d3a8cd2-bc3d-3b57-9e3d-0f2cf76dbef5},
 created = {2025-07-07T13:25:18.896Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:05.615Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Lundsgaard2018},
 private_publication = {false},
 bibtype = {article},
 author = {Lundsgaard, Anne-Marie and Holm, Jacob B. and Sjøberg, Kim A. and Bojsen-Møller, Kirstine N. and Myrmel, Lene S. and Fjære, Even and Jensen, Benjamin A.H. and Nicolaisen, Trine S. and Hingst, Janne R. and Hansen, Sine L. and Doll, Sophia and Geyer, Philip E. and Desmukh, Atul S. and Holst, Jens J. and Madsen, Lise and Kristiansen, Karsten and Wojtaszewski, Jørgen F.P. and Richter, Erik A. and Kiens, Bente},
 doi = {10.1016/j.cmet.2018.08.022},
 journal = {Cell Metabolism}
}

@article{
 title = {Prevotella-to-Bacteroides ratio predicts body weight and fat loss success on 24-week diets varying in macronutrient composition and dietary fiber: results from a post-hoc analysis.},
 type = {article},
 year = {2018},
 websites = {http://dx.doi.org/10.1038/s41366-018-0093-2},
 publisher = {Springer US},
 id = {ee8eb6fc-28df-398c-ad8f-b66855849eeb},
 created = {2025-07-07T13:25:19.227Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:05.959Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Hjorth2018},
 private_publication = {false},
 bibtype = {article},
 author = {Hjorth, Mads F and Blædel, Trine and Bendtsen, Line Quist and Lorenzen, Janne K. and Holm, Jacob B. and Kiilerich, Pia and Roager, Henrik M. and Kristiansen, Karsten and Larsen, Lesli H. and Astrup, Arne},
 doi = {(In press)},
 journal = {International Journal of Obesity}
}

@article{
 title = {Recovery of gut microbiota of healthy adults following antibiotic exposure},
 type = {article},
 year = {2018},
 pages = {1255-1265},
 volume = {3},
 websites = {http://www.nature.com/articles/s41564-018-0257-9},
 month = {11},
 day = {22},
 id = {36dd3c7c-7cf6-362d-8069-f7a059f1a586},
 created = {2025-07-07T13:25:19.562Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:06.298Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Palleja2018},
 private_publication = {false},
 bibtype = {article},
 author = {Palleja, Albert and Mikkelsen, Kristian H. and Forslund, Sofia K. and Kashani, Alireza and Allin, Kristine H. and Nielsen, Trine and Hansen, Tue H. and Liang, Suisha and Feng, Qiang and Zhang, Chenchen and Pyl, Paul Theodor and Coelho, Luis Pedro and Yang, Huanming and Wang, Jian and Typas, Athanasios and Nielsen, Morten F. and Nielsen, Henrik Bjorn and Bork, Peer and Wang, Jun and Vilsbøll, Tina and Hansen, Torben and Knop, Filip K. and Arumugam, Manimozhiyan and Pedersen, Oluf},
 doi = {10.1038/s41564-018-0257-9},
 journal = {Nature Microbiology},
 number = {11}
}

@article{
 title = {Recovery of gut microbiota of healthy adults following antibiotic exposure},
 type = {article},
 year = {2018},
 pages = {1255-1265},
 volume = {3},
 month = {11},
 publisher = {Nature Publishing Group},
 day = {1},
 id = {afff861f-5e70-3e4b-a67c-ad855282eb73},
 created = {2025-10-30T12:09:26.826Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:26.826Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {To minimize the impact of antibiotics, gut microorganisms harbour and exchange antibiotics resistance genes, collectively called their resistome. Using shotgun sequencing-based metagenomics, we analysed the partial eradication and subsequent regrowth of the gut microbiota in 12 healthy men over a 6-month period following a 4-day intervention with a cocktail of 3 last-resort antibiotics: meropenem, gentamicin and vancomycin. Initial changes included blooms of enterobacteria and other pathobionts, such as Enterococcus faecalis and Fusobacterium nucleatum, and the depletion of Bifidobacterium species and butyrate producers. The gut microbiota of the subjects recovered to near-baseline composition within 1.5 months, although 9 common species, which were present in all subjects before the treatment, remained undetectable in most of the subjects after 180 days. Species that harbour β-lactam resistance genes were positively selected for during and after the intervention. Harbouring glycopeptide or aminoglycoside resistance genes increased the odds of de novo colonization, however, the former also decreased the odds of survival. Compositional changes under antibiotic intervention in vivo matched results from in vitro susceptibility tests. Despite a mild yet long-lasting imprint following antibiotics exposure, the gut microbiota of healthy young adults are resilient to a short-term broad-spectrum antibiotics intervention and their antibiotics resistance gene carriage modulates their recovery processes.},
 bibtype = {article},
 author = {Palleja, Albert and Mikkelsen, Kristian H. and Forslund, Sofia K. and Kashani, Alireza and Allin, Kristine H. and Nielsen, Trine and Hansen, Tue H. and Liang, Suisha and Feng, Qiang and Zhang, Chenchen and Pyl, Paul Theodor and Coelho, Luis Pedro and Yang, Huanming and Wang, Jian and Typas, Athanasios and Nielsen, Morten F. and Nielsen, Henrik Bjorn and Bork, Peer and Wang, Jun and Vilsbøll, Tina and Hansen, Torben and Knop, Filip K. and Arumugam, Manimozhiyan and Pedersen, Oluf},
 doi = {10.1038/s41564-018-0257-9},
 journal = {Nature Microbiology},
 number = {11}
}

To minimize the impact of antibiotics, gut microorganisms harbour and exchange antibiotics resistance genes, collectively called their resistome. Using shotgun sequencing-based metagenomics, we analysed the partial eradication and subsequent regrowth of the gut microbiota in 12 healthy men over a 6-month period following a 4-day intervention with a cocktail of 3 last-resort antibiotics: meropenem, gentamicin and vancomycin. Initial changes included blooms of enterobacteria and other pathobionts, such as Enterococcus faecalis and Fusobacterium nucleatum, and the depletion of Bifidobacterium species and butyrate producers. The gut microbiota of the subjects recovered to near-baseline composition within 1.5 months, although 9 common species, which were present in all subjects before the treatment, remained undetectable in most of the subjects after 180 days. Species that harbour β-lactam resistance genes were positively selected for during and after the intervention. Harbouring glycopeptide or aminoglycoside resistance genes increased the odds of de novo colonization, however, the former also decreased the odds of survival. Compositional changes under antibiotic intervention in vivo matched results from in vitro susceptibility tests. Despite a mild yet long-lasting imprint following antibiotics exposure, the gut microbiota of healthy young adults are resilient to a short-term broad-spectrum antibiotics intervention and their antibiotics resistance gene carriage modulates their recovery processes.

@article{
 title = {Host genetics and the rumen microbiome jointly associate with methane emissions in dairy cows},
 type = {article},
 year = {2018},
 volume = {14},
 month = {10},
 publisher = {Public Library of Science},
 day = {1},
 id = {d2462cd6-fc70-3614-90b6-e9e6fa9655ba},
 created = {2025-10-30T12:09:26.851Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:30.167Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Cattle and other ruminants produce large quantities of methane (~110 million metric tonnes per annum), which is a potent greenhouse gas affecting global climate change. Methane (CH4) is a natural by-product of gastro-enteric microbial fermentation of feedstuffs in the rumen and contributes to 6% of total CH4 emissions from anthropogenic-related sources. The extent to which the host genome and rumen microbiome influence CH4 emission is not yet well known. This study confirms individual variation in CH4 production was influenced by individual host (cow) genotype, as well as the host’s rumen microbiome composition. Abundance of a small proportion of bacteria and archaea taxa were influenced to a limited extent by the host’s genotype and certain taxa were associated with CH4 emissions. However, the cumulative effect of all bacteria and archaea on CH4 production was 13%, the host genetics (heritability) was 21% and the two are largely independent. This study demonstrates variation in CH4 emission is likely not modulated through cow genetic effects on the rumen microbiome. Therefore, the rumen microbiome and cow genome could be targeted independently, by breeding low methane-emitting cows and in parallel, by investigating possible strategies that target changes in the rumen microbiome to reduce CH4 emissions in the cattle industry.},
 bibtype = {article},
 author = {Difford, Gareth Frank and Plichta, Damian Rafal and Løvendahl, Peter and Lassen, Jan and Noel, Samantha Joan and Højberg, Ole and Wright, André Denis G. and Zhu, Zhigang and Kristensen, Lise and Nielsen, Henrik Bjørn and Guldbrandtsen, Bernt and Sahana, Goutam},
 doi = {10.1371/journal.pgen.1007580},
 journal = {PLoS Genetics},
 number = {10}
}

Cattle and other ruminants produce large quantities of methane (~110 million metric tonnes per annum), which is a potent greenhouse gas affecting global climate change. Methane (CH4) is a natural by-product of gastro-enteric microbial fermentation of feedstuffs in the rumen and contributes to 6% of total CH4 emissions from anthropogenic-related sources. The extent to which the host genome and rumen microbiome influence CH4 emission is not yet well known. This study confirms individual variation in CH4 production was influenced by individual host (cow) genotype, as well as the host’s rumen microbiome composition. Abundance of a small proportion of bacteria and archaea taxa were influenced to a limited extent by the host’s genotype and certain taxa were associated with CH4 emissions. However, the cumulative effect of all bacteria and archaea on CH4 production was 13%, the host genetics (heritability) was 21% and the two are largely independent. This study demonstrates variation in CH4 emission is likely not modulated through cow genetic effects on the rumen microbiome. Therefore, the rumen microbiome and cow genome could be targeted independently, by breeding low methane-emitting cows and in parallel, by investigating possible strategies that target changes in the rumen microbiome to reduce CH4 emissions in the cattle industry.

@article{
 title = {A computational framework to integrate high-throughput ‘-omics’ datasets for the identification of potential mechanistic links},
 type = {article},
 year = {2018},
 pages = {2781-2800},
 volume = {13},
 month = {12},
 publisher = {Nature Publishing Group},
 day = {1},
 id = {d50b2e2c-189f-3dfb-a497-d7a0d27990e4},
 created = {2025-10-30T12:09:26.865Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:26.865Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {We recently presented a three-pronged association study that integrated human intestinal microbiome data derived from shotgun-based sequencing with untargeted serum metabolome data and measures of host physiology. Metabolome and microbiome data are high dimensional, posing a major challenge for data integration. Here, we present a step-by-step computational protocol that details and discusses the dimensionality-reduction techniques used and methods for subsequent integration and interpretation of such heterogeneous types of data. Dimensionality reduction was achieved through a combination of data normalization approaches, binning of co-abundant genes and metabolites, and integration of prior biological knowledge. The use of prior knowledge to overcome functional redundancy across microbiome species is one central advance of our method over available alternative approaches. Applying this framework, other investigators can integrate various ‘-omics’ readouts with variables of host physiology or any other phenotype of interest (e.g., connecting host and microbiome readouts to disease severity or treatment outcome in a clinical cohort) in a three-pronged association analysis to identify potential mechanistic links to be tested in experimental settings. Although we originally developed the framework for a human metabolome–microbiome study, it is generalizable to other organisms and environmental metagenomes, as well as to studies including other -omics domains such as transcriptomics and proteomics. The provided R code runs in ~1 h on a standard PC.},
 bibtype = {article},
 author = {Pedersen, Helle Krogh and Forslund, Sofia K. and Gudmundsdottir, Valborg and Petersen, Anders Østergaard and Hildebrand, Falk and Hyötyläinen, Tuulia and Nielsen, Trine and Hansen, Torben and Bork, Peer and Ehrlich, S. Dusko and Brunak, Søren and Oresic, Matej and Pedersen, Oluf and Nielsen, Henrik Bjørn},
 doi = {10.1038/s41596-018-0064-z},
 journal = {Nature Protocols},
 number = {12}
}

We recently presented a three-pronged association study that integrated human intestinal microbiome data derived from shotgun-based sequencing with untargeted serum metabolome data and measures of host physiology. Metabolome and microbiome data are high dimensional, posing a major challenge for data integration. Here, we present a step-by-step computational protocol that details and discusses the dimensionality-reduction techniques used and methods for subsequent integration and interpretation of such heterogeneous types of data. Dimensionality reduction was achieved through a combination of data normalization approaches, binning of co-abundant genes and metabolites, and integration of prior biological knowledge. The use of prior knowledge to overcome functional redundancy across microbiome species is one central advance of our method over available alternative approaches. Applying this framework, other investigators can integrate various ‘-omics’ readouts with variables of host physiology or any other phenotype of interest (e.g., connecting host and microbiome readouts to disease severity or treatment outcome in a clinical cohort) in a three-pronged association analysis to identify potential mechanistic links to be tested in experimental settings. Although we originally developed the framework for a human metabolome–microbiome study, it is generalizable to other organisms and environmental metagenomes, as well as to studies including other -omics domains such as transcriptomics and proteomics. The provided R code runs in ~1 h on a standard PC.

@article{
 title = {A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults},
 type = {article},
 year = {2018},
 volume = {9},
 month = {12},
 publisher = {Nature Publishing Group},
 day = {1},
 id = {b6f2b425-0661-357b-8a7a-e8fe628f3e10},
 created = {2025-10-30T12:09:26.966Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:31.047Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.},
 bibtype = {article},
 author = {Hansen, Lea B.S. and Roager, Henrik M. and Søndertoft, Nadja B. and Gøbel, Rikke J. and Kristensen, Mette and Vallès-Colomer, Mireia and Vieira-Silva, Sara and Ibrügger, Sabine and Lind, Mads V. and Mærkedahl, Rasmus B. and Bahl, Martin I. and Madsen, Mia L. and Havelund, Jesper and Falony, Gwen and Tetens, Inge and Nielsen, Trine and Allin, Kristine H. and Frandsen, Henrik L. and Hartmann, Bolette and Holst, Jens Juul and Sparholt, Morten H. and Holck, Jesper and Blennow, Andreas and Moll, Janne Marie and Meyer, Anne S. and Hoppe, Camilla and Poulsen, Jørgen H. and Carvalho, Vera and Sagnelli, Domenico and Dalgaard, Marlene D. and Christensen, Anders F. and Lydolph, Magnus Christian and Ross, Alastair B. and Villas-Bôas, Silas and Brix, Susanne and Sicheritz-Pontén, Thomas and Buschard, Karsten and Linneberg, Allan and Rumessen, Jüri J. and Ekstrøm, Claus T. and Ritz, Christian and Kristiansen, Karsten and Nielsen, H. Bjørn and Vestergaard, Henrik and Færgeman, Nils J. and Raes, Jeroen and Frøkiær, Hanne and Hansen, Torben and Lauritzen, Lotte and Gupta, Ramneek and Licht, Tine Rask and Pedersen, Oluf},
 doi = {10.1038/s41467-018-07019-x},
 journal = {Nature Communications},
 number = {1}
}

Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.

@article{
 title = {Distinct consequences of amoxicillin and ertapenem exposure in the porcine gut microbiome},
 type = {article},
 year = {2018},
 keywords = {Antibiotic,Antibiotic resistance,Dysbiosis,Microbiome,Porcine},
 pages = {82-93},
 volume = {53},
 month = {10},
 publisher = {Academic Press},
 day = {1},
 id = {ff6796bf-1cd0-3896-b253-fd9307852f7f},
 created = {2025-10-30T12:26:00.975Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.975Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The gut microbiome influences many, if not all, aspects of human health. Antibiotics, while lifesaving, have the unintended consequence of killing commensal microbiota inhabiting the gastrointestinal (GI) tract, which can lead to overgrowth of opportunistic pathogens such as Clostridium difficile and emergence of antibiotic-resistant organisms. Here, porcine models were developed to evaluate changes to the gut microbiome caused by two distinct types of beta-lactam antibiotics delivered via common administration routes, oral amoxicillin and intravenous ertapenem. Amoxicillin is one of the most often used broad-spectrum antibiotics, frequently prescribed to young children. Ertapenem, a carbapenem considered a last resort antibiotic, is used sparingly in humans and prohibited for use in animals. Cohorts of normal pigs (n = 5) were treated with amoxicillin (20 mg/kg, PO, BID) or ertapenem (30 mg/kg, IV, SID) for seven days. Microbiomes were evaluated using whole genome shotgun metagenomics analyses of fecal DNA collected prior to, during, and after antibiotic treatment. Each antibiotic resulted in significant and distinct changes in the microbiome, causing elimination of key commensal bacterial species and overgrowth of other, potentially pathogenic taxa. In addition, amoxicillin promoted propagation of a broad range of antibiotic resistance genes, many encoding efflux pump components and beta-lactamases, while ertapenem triggered emergence of genes encoding vancomycin resistance, and beta-lactamases, including the carbapenemase, IMP-27. Notably, microbiota alterations and antibiotic resistance gene propagation displayed unique patterns following exposure to amoxicillin or ertapenem. These data underscore the importance of understanding consequences of individual antibiotic use to predict and potentially mitigate adverse outcomes. The porcine models developed here can facilitate evaluation of therapeutic interventions to prevent antibiotic-mediated microbiome disruption.},
 bibtype = {article},
 author = {Connelly, Sheila and Subramanian, Poorani and Hasan, Nur A. and Colwell, Rita R. and Kaleko, Michael},
 doi = {10.1016/J.ANAEROBE.2018.04.012},
 journal = {Anaerobe}
}

The gut microbiome influences many, if not all, aspects of human health. Antibiotics, while lifesaving, have the unintended consequence of killing commensal microbiota inhabiting the gastrointestinal (GI) tract, which can lead to overgrowth of opportunistic pathogens such as Clostridium difficile and emergence of antibiotic-resistant organisms. Here, porcine models were developed to evaluate changes to the gut microbiome caused by two distinct types of beta-lactam antibiotics delivered via common administration routes, oral amoxicillin and intravenous ertapenem. Amoxicillin is one of the most often used broad-spectrum antibiotics, frequently prescribed to young children. Ertapenem, a carbapenem considered a last resort antibiotic, is used sparingly in humans and prohibited for use in animals. Cohorts of normal pigs (n = 5) were treated with amoxicillin (20 mg/kg, PO, BID) or ertapenem (30 mg/kg, IV, SID) for seven days. Microbiomes were evaluated using whole genome shotgun metagenomics analyses of fecal DNA collected prior to, during, and after antibiotic treatment. Each antibiotic resulted in significant and distinct changes in the microbiome, causing elimination of key commensal bacterial species and overgrowth of other, potentially pathogenic taxa. In addition, amoxicillin promoted propagation of a broad range of antibiotic resistance genes, many encoding efflux pump components and beta-lactamases, while ertapenem triggered emergence of genes encoding vancomycin resistance, and beta-lactamases, including the carbapenemase, IMP-27. Notably, microbiota alterations and antibiotic resistance gene propagation displayed unique patterns following exposure to amoxicillin or ertapenem. These data underscore the importance of understanding consequences of individual antibiotic use to predict and potentially mitigate adverse outcomes. The porcine models developed here can facilitate evaluation of therapeutic interventions to prevent antibiotic-mediated microbiome disruption.

@article{
 title = {Spores and soil from six sides: interdisciplinarity and the environmental biology of anthrax (Bacillus anthracis)},
 type = {article},
 year = {2018},
 keywords = {Bacillus anthracis,Bacillus cereus,Etosha National Park,anthrax,disease ecology,eco-epidemiology,environmental transmission,interdisciplinarity},
 pages = {1813-1831},
 volume = {93},
 month = {11},
 publisher = {Blackwell Publishing Ltd},
 day = {1},
 id = {73a47185-c888-39e2-bfc3-9f013ea10f45},
 created = {2025-10-30T12:26:01.000Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.000Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Environmentally transmitted diseases are comparatively poorly understood and managed, and their ecology is particularly understudied. Here we identify challenges of studying environmental transmission and persistence with a six-sided interdisciplinary review of the biology of anthrax (Bacillus anthracis). Anthrax is a zoonotic disease capable of maintaining infectious spore banks in soil for decades (or even potentially centuries), and the mechanisms of its environmental persistence have been the topic of significant research and controversy. Where anthrax is endemic, it plays an important ecological role, shaping the dynamics of entire herbivore communities. The complex eco-epidemiology of anthrax, and the mysterious biology of Bacillus anthracis during its environmental stage, have necessitated an interdisciplinary approach to pathogen research. Here, we illustrate different disciplinary perspectives through key advances made by researchers working in Etosha National Park, a long-term ecological research site in Namibia that has exemplified the complexities of the enzootic process of anthrax over decades of surveillance. In Etosha, the role of scavengers and alternative routes (waterborne transmission and flies) has proved unimportant relative to the long-term persistence of anthrax spores in soil and their infection of herbivore hosts. Carcass deposition facilitates green-ups of vegetation to attract herbivores, potentially facilitated by the role of anthrax spores in the rhizosphere. The underlying seasonal pattern of vegetation, and herbivores' immune and behavioural responses to anthrax risk, interact to produce regular ‘anthrax seasons’ that appear to be a stable feature of the Etosha ecosystem. Through the lens of microbiologists, geneticists, immunologists, ecologists, epidemiologists, and clinicians, we discuss how anthrax dynamics are shaped at the smallest scale by population genetics and interactions within the bacterial communities up to the broadest scales of ecosystem structure. We illustrate the benefits and challenges of this interdisciplinary approach to disease ecology, and suggest ways anthrax might offer insights into the biology of other important pathogens. Bacillus anthracis, and the more recently emerged Bacillus cereus biovar anthracis, share key features with other environmentally transmitted pathogens, including several zoonoses and panzootics of special interest for global health and conservation efforts. Understanding the dynamics of anthrax, and developing interdisciplinary research programs that explore environmental persistence, is a critical step forward for understanding these emerging threats.},
 bibtype = {article},
 author = {Carlson, Colin J. and Getz, Wayne M. and Kausrud, Kyrre L. and Cizauskas, Carrie A. and Blackburn, Jason K. and Bustos Carrillo, Fausto A. and Colwell, Rita and Easterday, W. Ryan and Ganz, Holly H. and Kamath, Pauline L. and Økstad, Ole A. and Turner, Wendy C. and Kolstø, Anne Brit and Stenseth, Nils C.},
 doi = {10.1111/BRV.12420},
 journal = {Biological Reviews},
 number = {4}
}

Environmentally transmitted diseases are comparatively poorly understood and managed, and their ecology is particularly understudied. Here we identify challenges of studying environmental transmission and persistence with a six-sided interdisciplinary review of the biology of anthrax (Bacillus anthracis). Anthrax is a zoonotic disease capable of maintaining infectious spore banks in soil for decades (or even potentially centuries), and the mechanisms of its environmental persistence have been the topic of significant research and controversy. Where anthrax is endemic, it plays an important ecological role, shaping the dynamics of entire herbivore communities. The complex eco-epidemiology of anthrax, and the mysterious biology of Bacillus anthracis during its environmental stage, have necessitated an interdisciplinary approach to pathogen research. Here, we illustrate different disciplinary perspectives through key advances made by researchers working in Etosha National Park, a long-term ecological research site in Namibia that has exemplified the complexities of the enzootic process of anthrax over decades of surveillance. In Etosha, the role of scavengers and alternative routes (waterborne transmission and flies) has proved unimportant relative to the long-term persistence of anthrax spores in soil and their infection of herbivore hosts. Carcass deposition facilitates green-ups of vegetation to attract herbivores, potentially facilitated by the role of anthrax spores in the rhizosphere. The underlying seasonal pattern of vegetation, and herbivores' immune and behavioural responses to anthrax risk, interact to produce regular ‘anthrax seasons’ that appear to be a stable feature of the Etosha ecosystem. Through the lens of microbiologists, geneticists, immunologists, ecologists, epidemiologists, and clinicians, we discuss how anthrax dynamics are shaped at the smallest scale by population genetics and interactions within the bacterial communities up to the broadest scales of ecosystem structure. We illustrate the benefits and challenges of this interdisciplinary approach to disease ecology, and suggest ways anthrax might offer insights into the biology of other important pathogens. Bacillus anthracis, and the more recently emerged Bacillus cereus biovar anthracis, share key features with other environmentally transmitted pathogens, including several zoonoses and panzootics of special interest for global health and conservation efforts. Understanding the dynamics of anthrax, and developing interdisciplinary research programs that explore environmental persistence, is a critical step forward for understanding these emerging threats.

@article{
 title = {A metagenomic approach to evaluating surface water quality in Haiti},
 type = {article},
 year = {2018},
 keywords = {Bioinformatics,Cholera,Environmental sampling,Haiti,Metagenomic analysis,Principle components analysis,Water quality,Whole genome sequencing},
 volume = {15},
 month = {10},
 publisher = {MDPI},
 day = {10},
 id = {37dbd503-546c-318d-a721-d52ea5881dc7},
 created = {2025-10-30T12:26:01.003Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:07.037Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The cholera epidemic that occurred in Haiti post-earthquake in 2010 has resulted in over 9000 deaths during the past eight years. Currently, morbidity and mortality rates for cholera have declined, but cholera cases still occur on a daily basis. One continuing issue is an inability to accurately predict and identify when cholera outbreaks might occur. To explore this surveillance gap, a metagenomic approach employing environmental samples was taken. In this study, surface water samples were collected at two time points from several sites near the original epicenter of the cholera outbreak in the Central Plateau of Haiti. These samples underwent whole genome sequencing and subsequent metagenomic analysis to characterize the microbial community of bacteria, fungi, protists, and viruses, and to identify antibiotic resistance and virulence associated genes. Replicates from sites were analyzed by principle components analysis, and distinct genomic profiles were obtained for each site. Cholera toxin converting phage was detected at one site, and Shiga toxin converting phages at several sites. Members of the Acinetobacter family were frequently detected in samples, including members implicated in waterborne diseases. These results indicate a metagenomic approach to evaluating water samples can be useful for source tracking and the surveillance of pathogens such as Vibrio cholerae over time, as well as for monitoring virulence factors such as cholera toxin.},
 bibtype = {article},
 author = {Roy, Monika A. and Arnaud, Jean M. and Jasmin, Paul M. and Hamner, Steve and Hasan, Nur A. and Colwell, Rita R. and Ford, Timothy E.},
 doi = {10.3390/IJERPH15102211},
 journal = {International Journal of Environmental Research and Public Health},
 number = {10}
}

The cholera epidemic that occurred in Haiti post-earthquake in 2010 has resulted in over 9000 deaths during the past eight years. Currently, morbidity and mortality rates for cholera have declined, but cholera cases still occur on a daily basis. One continuing issue is an inability to accurately predict and identify when cholera outbreaks might occur. To explore this surveillance gap, a metagenomic approach employing environmental samples was taken. In this study, surface water samples were collected at two time points from several sites near the original epicenter of the cholera outbreak in the Central Plateau of Haiti. These samples underwent whole genome sequencing and subsequent metagenomic analysis to characterize the microbial community of bacteria, fungi, protists, and viruses, and to identify antibiotic resistance and virulence associated genes. Replicates from sites were analyzed by principle components analysis, and distinct genomic profiles were obtained for each site. Cholera toxin converting phage was detected at one site, and Shiga toxin converting phages at several sites. Members of the Acinetobacter family were frequently detected in samples, including members implicated in waterborne diseases. These results indicate a metagenomic approach to evaluating water samples can be useful for source tracking and the surveillance of pathogens such as Vibrio cholerae over time, as well as for monitoring virulence factors such as cholera toxin.

@article{
 title = {Environmental and hydroclimatic factors influencing Vibrio populations in the estuarine zone of the Bengal delta},
 type = {article},
 year = {2018},
 keywords = {Chitin,Cyclone,Salinity,Sediment dynamics,Tide,Vibrio},
 volume = {190},
 month = {10},
 publisher = {Springer International Publishing},
 day = {1},
 id = {f039d582-be17-3e14-915e-84cdf01b281e},
 created = {2025-10-30T12:26:01.004Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.004Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The objective of this study was to determine environmental parameters driving Vibrio populations in the estuarine zone of the Bengal delta. Spatio-temporal data were collected at river estuary, mangrove, beach, pond, and canal sites. Effects of salinity, tidal amplitude, and a cyclone and tsunami were included in the study. Vibrio population shifts were found to be correlated with tide-driven salinity and suspended particulate matter (SPM). Increased abundance of Vibrio spp. in surface water was observed after a cyclone, attributed to re-suspension of benthic particulate organic carbon (POC), and increased availability of chitin and dissolved organic carbon (DOC). Approximately a two log10 increase in the (p < 0.05) number of Vibrio spp. was observed in < 20 μm particulates, compared with microphytoplankton (20–60 μm) and zooplankton > 60 μm fractions. Benthic and suspended sediment comprised a major reservoir of Vibrio spp. Results of microcosm experiments showed enhanced growth of vibrios was related to concentration of organic matter in SPM. It is concluded that SPM, POC, chitin, and salinity significantly influence abundance and distribution of vibrios in the Bengal delta estuarine zone.},
 bibtype = {article},
 author = {Neogi, Sucharit Basu and Lara, Rubén and Alam, Munirul and Harder, Jens and Yamasaki, Shinji and Colwell, Rita R.},
 doi = {10.1007/S10661-018-6925-7},
 journal = {Environmental Monitoring and Assessment},
 number = {10}
}

The objective of this study was to determine environmental parameters driving Vibrio populations in the estuarine zone of the Bengal delta. Spatio-temporal data were collected at river estuary, mangrove, beach, pond, and canal sites. Effects of salinity, tidal amplitude, and a cyclone and tsunami were included in the study. Vibrio population shifts were found to be correlated with tide-driven salinity and suspended particulate matter (SPM). Increased abundance of Vibrio spp. in surface water was observed after a cyclone, attributed to re-suspension of benthic particulate organic carbon (POC), and increased availability of chitin and dissolved organic carbon (DOC). Approximately a two log10 increase in the (p < 0.05) number of Vibrio spp. was observed in < 20 μm particulates, compared with microphytoplankton (20–60 μm) and zooplankton > 60 μm fractions. Benthic and suspended sediment comprised a major reservoir of Vibrio spp. Results of microcosm experiments showed enhanced growth of vibrios was related to concentration of organic matter in SPM. It is concluded that SPM, POC, chitin, and salinity significantly influence abundance and distribution of vibrios in the Bengal delta estuarine zone.

@article{
 title = {Comparison of infant gut and skin microbiota, resistome and virulome between neonatal intensive care unit (NICU) environments},
 type = {article},
 year = {2018},
 keywords = {Environment,Microbiome,Microbiota,NICU,Neonatal,Resistome,Virulome},
 volume = {9},
 month = {6},
 publisher = {Frontiers Media S.A.},
 day = {25},
 id = {a68e25bc-94c9-3856-a7fa-98f857fbaf2e},
 created = {2025-10-30T12:26:01.017Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:09.293Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: There is a growing move to provide care for premature infants in a single family, private room neonatal intensive care unit (NICU) in place of the traditional shared space, open bay NICU. The resultant effect on the developing neonatal microbiota is unknown. Study Design: Stool and groin skin swabs were collected from infants in a shared-space NICU (old NICU) and a single-family room NICU (new NICU) on the same hospital campus. Metagenomic sequencing was performed and data analyzed by CosmosID bioinformatics software package. Results: There were no significant differences between the cohorts in gestational age, length of stay, and delivery mode; infants in the old NICU received significantly more antibiotics (p = 0.03). Differentially abundant antimicrobial resistance genes and virulence associated genes were found between the cohorts in stool and skin, with more differentially abundant antimicrobial resistance genes in the new NICU. The entire bacterial microbiota analyzed to the genus level significantly differed between cohorts in skin (p = 0.0001) but not in stool samples. There was no difference in alpha diversity between the two cohorts. DNA viruses and fungi were detected but did not differ between cohorts. Conclusion: Differences were seen in the resistome and virulome between the two cohorts with more differentially abundant antimicrobial resistance genes in the new NICU. This highlights the influence that different NICU environments can have on the neonatal microbiota. Whether the differences were due to the new NICU being a single-family NICU or located in a newly constructed building warrants exploration. Long term health outcomes from the differences observed must be followed longitudinally.},
 bibtype = {article},
 author = {Hourigan, Suchitra K. and Subramanian, Poorani and Hasan, Nur A. and Ta, Allison and Klein, Elisabeth and Chettout, Nassim and Huddleston, Kathi and Deopujari, Varsha and Levy, Shira and Baveja, Rajiv and Clemency, Nicole C. and Baker, Robin L. and Niederhuber, John E. and Colwell, Rita R.},
 doi = {10.3389/FMICB.2018.01361},
 journal = {Frontiers in Microbiology},
 number = {JUN}
}

Background: There is a growing move to provide care for premature infants in a single family, private room neonatal intensive care unit (NICU) in place of the traditional shared space, open bay NICU. The resultant effect on the developing neonatal microbiota is unknown. Study Design: Stool and groin skin swabs were collected from infants in a shared-space NICU (old NICU) and a single-family room NICU (new NICU) on the same hospital campus. Metagenomic sequencing was performed and data analyzed by CosmosID bioinformatics software package. Results: There were no significant differences between the cohorts in gestational age, length of stay, and delivery mode; infants in the old NICU received significantly more antibiotics (p = 0.03). Differentially abundant antimicrobial resistance genes and virulence associated genes were found between the cohorts in stool and skin, with more differentially abundant antimicrobial resistance genes in the new NICU. The entire bacterial microbiota analyzed to the genus level significantly differed between cohorts in skin (p = 0.0001) but not in stool samples. There was no difference in alpha diversity between the two cohorts. DNA viruses and fungi were detected but did not differ between cohorts. Conclusion: Differences were seen in the resistome and virulome between the two cohorts with more differentially abundant antimicrobial resistance genes in the new NICU. This highlights the influence that different NICU environments can have on the neonatal microbiota. Whether the differences were due to the new NICU being a single-family NICU or located in a newly constructed building warrants exploration. Long term health outcomes from the differences observed must be followed longitudinally.

@article{
 title = {Current progress and future opportunities in applications of bioinformatics for biodefense and pathogen detection: Report from the Winter Mid-Atlantic Microbiome Meet-up, College Park, MD, January 10, 2018},
 type = {article},
 year = {2018},
 keywords = {Biodefense,Bioinformatics,Biothreats,Longitudinal analysis,Metagenomics,Microbiome,Pathogen detection},
 volume = {6},
 month = {11},
 publisher = {BioMed Central Ltd.},
 day = {5},
 id = {ceab4777-8716-364a-8074-4591e3a4371d},
 created = {2025-10-30T12:26:01.191Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:07.038Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The Mid-Atlantic Microbiome Meet-up (M 3 ) organization brings together academic, government, and industry groups to share ideas and develop best practices for microbiome research. In January of 2018, M 3 held its fourth meeting, which focused on recent advances in biodefense, specifically those relating to infectious disease, and the use of metagenomic methods for pathogen detection. Presentations highlighted the utility of next-generation sequencing technologies for identifying and tracking microbial community members across space and time. However, they also stressed the current limitations of genomic approaches for biodefense, including insufficient sensitivity to detect low-abundance pathogens and the inability to quantify viable organisms. Participants discussed ways in which the community can improve software usability and shared new computational tools for metagenomic processing, assembly, annotation, and visualization. Looking to the future, they identified the need for better bioinformatics toolkits for longitudinal analyses, improved sample processing approaches for characterizing viruses and fungi, and more consistent maintenance of database resources. Finally, they addressed the necessity of improving data standards to incentivize data sharing. Here, we summarize the presentations and discussions from the meeting, identifying the areas where microbiome analyses have improved our ability to detect and manage biological threats and infectious disease, as well as gaps of knowledge in the field that require future funding and focus.},
 bibtype = {article},
 author = {Meisel, Jacquelyn S. and Nasko, Daniel J. and Brubach, Brian and Cepeda-Espinoza, Victoria and Chopyk, Jessica and Corrada-Bravo, Héctor and Fedarko, Marcus and Ghurye, Jay and Javkar, Kiran and Olson, Nathan D. and Shah, Nidhi and Allard, Sarah M. and Bazinet, Adam L. and Bergman, Nicholas H. and Brown, Alexis and Caporaso, J. Gregory and Conlan, Sean and Diruggiero, Jocelyne and Forry, Samuel P. and Hasan, Nur A. and Kralj, Jason and Luethy, Paul M. and Milton, Donald K. and Ondov, Brian D. and Preheim, Sarah and Ratnayake, Shashikala and Rogers, Stephanie M. and Rosovitz, M. J. and Sakowski, Eric G. and Schliebs, Nils Oliver and Sommer, Daniel D. and Ternus, Krista L. and Uritskiy, Gherman and Zhang, Sean X. and Pop, Mihai and Treangen, Todd J.},
 doi = {10.1186/S40168-018-0582-5},
 journal = {Microbiome},
 number = {1}
}

The Mid-Atlantic Microbiome Meet-up (M 3 ) organization brings together academic, government, and industry groups to share ideas and develop best practices for microbiome research. In January of 2018, M 3 held its fourth meeting, which focused on recent advances in biodefense, specifically those relating to infectious disease, and the use of metagenomic methods for pathogen detection. Presentations highlighted the utility of next-generation sequencing technologies for identifying and tracking microbial community members across space and time. However, they also stressed the current limitations of genomic approaches for biodefense, including insufficient sensitivity to detect low-abundance pathogens and the inability to quantify viable organisms. Participants discussed ways in which the community can improve software usability and shared new computational tools for metagenomic processing, assembly, annotation, and visualization. Looking to the future, they identified the need for better bioinformatics toolkits for longitudinal analyses, improved sample processing approaches for characterizing viruses and fungi, and more consistent maintenance of database resources. Finally, they addressed the necessity of improving data standards to incentivize data sharing. Here, we summarize the presentations and discussions from the meeting, identifying the areas where microbiome analyses have improved our ability to detect and manage biological threats and infectious disease, as well as gaps of knowledge in the field that require future funding and focus.

@article{
 title = {Characterization of the microbiome at the world's largest potable water reuse facility},
 type = {article},
 year = {2018},
 keywords = {Metagenomics,Metatranscriptomics,Pathogens,Water Purification,Water reuse},
 volume = {9},
 month = {10},
 publisher = {Frontiers Media S.A.},
 day = {26},
 id = {72ba57b7-60ec-3340-a544-f434bc0dddf3},
 created = {2025-10-30T12:26:02.105Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:02.105Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Conventional water resources are not sufficient in many regions to meet the needs of growing populations. Due to cyclical weather cycles, drought, and climate change, water stress has increased worldwide including in Southern California, which serves as a model for regions that integrate reuse of wastewater for both potable and non-potable use. The Orange County Water District (OCWD) Advanced Water Purification Facility (AWPF) is a highly engineered system designed to treat and produce up to 100 million gallons per day (MGD) of purified water from a municipal wastewater source for potable reuse. Routine facility microbial water quality analysis is limited to standard indicators at this and similar facilities. Given recent advances in high throughput DNA sequencing techniques, complete microbial profiling of communities in water samples is now possible. By using 16S/18S rRNA gene sequencing, metagenomic and metatranscriptomic sequencing coupled to a highly accurate identification method along with 16S rRNA gene qPCR, we describe a detailed view of the total microbial community throughout the facility. The total bacterial load of the water at stages of the treatment train ranged from 3.02 × 106 copies in source, unchlorinated wastewater feed to 5.49 × 101 copies of 16S rRNA gene/mL after treatment (consisting of microfiltration, reverse osmosis, and ultraviolet/advanced oxidation). Microbial diversity and load decreased by several orders of magnitude after microfiltration and reverse osmosis treatment, falling to almost non-detectable levels that more closely resembled controls of molecular grade laboratory water than the biomass detected in the source water. The presence of antibiotic resistance genes and viruses was also greatly reduced. Overall, system design performance was achieved, and comprehensive microbial community analysis was found to enable a more complete characterization of the water/wastewater microbial signature.},
 bibtype = {article},
 author = {Stamps, Blake W. and Leddy, Menu B. and Plumlee, Megan H. and Hasan, Nur A. and Colwell, Rita R. and Spear, John R.},
 doi = {10.3389/FMICB.2018.02435},
 journal = {Frontiers in Microbiology},
 number = {OCT}
}

Conventional water resources are not sufficient in many regions to meet the needs of growing populations. Due to cyclical weather cycles, drought, and climate change, water stress has increased worldwide including in Southern California, which serves as a model for regions that integrate reuse of wastewater for both potable and non-potable use. The Orange County Water District (OCWD) Advanced Water Purification Facility (AWPF) is a highly engineered system designed to treat and produce up to 100 million gallons per day (MGD) of purified water from a municipal wastewater source for potable reuse. Routine facility microbial water quality analysis is limited to standard indicators at this and similar facilities. Given recent advances in high throughput DNA sequencing techniques, complete microbial profiling of communities in water samples is now possible. By using 16S/18S rRNA gene sequencing, metagenomic and metatranscriptomic sequencing coupled to a highly accurate identification method along with 16S rRNA gene qPCR, we describe a detailed view of the total microbial community throughout the facility. The total bacterial load of the water at stages of the treatment train ranged from 3.02 × 106 copies in source, unchlorinated wastewater feed to 5.49 × 101 copies of 16S rRNA gene/mL after treatment (consisting of microfiltration, reverse osmosis, and ultraviolet/advanced oxidation). Microbial diversity and load decreased by several orders of magnitude after microfiltration and reverse osmosis treatment, falling to almost non-detectable levels that more closely resembled controls of molecular grade laboratory water than the biomass detected in the source water. The presence of antibiotic resistance genes and viruses was also greatly reduced. Overall, system design performance was achieved, and comprehensive microbial community analysis was found to enable a more complete characterization of the water/wastewater microbial signature.

@article{
 title = {A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis},
 type = {article},
 year = {2017},
 keywords = {Bacterial genes,Dysbiosis,Metagenomics},
 pages = {1-12},
 volume = {7},
 websites = {https://www.nature.com/articles/s41598-017-06880-y},
 month = {7},
 publisher = {Nature Publishing Group},
 day = {27},
 id = {7dc59654-aeaf-3868-b402-21942434f060},
 created = {2025-07-07T13:25:13.387Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:00.616Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Cystic Fibrosis (CF) and its treatment result in an altered gut microbiota composition compared to non-CF controls. However, the impact of this on gut microbiota functionality has not been extensively characterised. Our aim was to conduct a proof-of-principle study to investigate if measurable changes in gut microbiota functionality occur in adult CF patients compared to controls. Metagenomic DNA was extracted from faecal samples from six CF patients and six non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq platform. Metabolomic analysis using gas chromatography-mass spectrometry was conducted on faecal water. The gut microbiota of the CF group was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430 meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared to the controls. Significant differences in metabolites occurred between the two groups. This proof-of-principle study demonstrates that measurable changes in gut microbiota functionality occur in CF patients compared to controls. Larger studies are thus needed to interrogate this further.},
 bibtype = {article},
 author = {Fouhy, F. and Ronan, N. J. and O'Sullivan, O. and McCarthy, Y. and Walsh, A. M. and Murphy, D. M. and Daly, M. and Flanagan, E. T. and Fleming, C. and McCarthy, M. and Shortt, C. and Eustace, J. A. and Shanahan, F. and Rea, M. C. and Ross, R. P. and Stanton, C. and Plant, B. J.},
 doi = {10.1038/s41598-017-06880-y},
 journal = {Scientific Reports 2017 7:1},
 number = {1}
}

Cystic Fibrosis (CF) and its treatment result in an altered gut microbiota composition compared to non-CF controls. However, the impact of this on gut microbiota functionality has not been extensively characterised. Our aim was to conduct a proof-of-principle study to investigate if measurable changes in gut microbiota functionality occur in adult CF patients compared to controls. Metagenomic DNA was extracted from faecal samples from six CF patients and six non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq platform. Metabolomic analysis using gas chromatography-mass spectrometry was conducted on faecal water. The gut microbiota of the CF group was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430 meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared to the controls. Significant differences in metabolites occurred between the two groups. This proof-of-principle study demonstrates that measurable changes in gut microbiota functionality occur in CF patients compared to controls. Larger studies are thus needed to interrogate this further.

@article{
 title = {Conversion of glycerol to 3-hydroxypropanoic acid by genetically engineered Bacillus subtilis},
 type = {article},
 year = {2017},
 keywords = {3-hydroxypropanoic acid,Bacillus subtilis,Glycerol,Glycerol kinase knock-out,Metabolic engineering},
 pages = {254491},
 volume = {8},
 websites = {www.frontiersin.org},
 month = {4},
 publisher = {Frontiers Research Foundation},
 day = {18},
 id = {c560c7a4-d3f7-30df-b8b8-57505ba237a0},
 created = {2025-07-07T13:25:13.745Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:01.012Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {3-Hydroxypropanoic acid (3-HP) is an important biomass-derivable platform chemical that can be converted into a number of industrially relevant compounds. There have been several attempts to produce 3-HP from renewable sources in cell factories, focusing mainly on Escherichia coli, Klebsiella pneumoniae, and Saccharomyces cerevisiae. Despite the significant progress made in this field, commercially exploitable large-scale production of 3-HP in microbial strains has still not been achieved. In this study, we investigated the potential of Bacillus subtilis as a microbial platform for bioconversion of glycerol into 3-HP. Our recombinant B. subtilis strains overexpress the two-step heterologous pathway containing glycerol dehydratase and aldehyde dehydrogenase from K. pneumoniae. Genetic engineering, driven by in silico optimization, and optimization of cultivation conditions resulted in a 3-HP titer of 10 g/L, in a standard batch cultivation. Our findings provide the first report of successful introduction of the biosynthetic pathway for conversion of glycerol into 3-HP in B. subtilis. With this relatively high titer in batch, and the robustness of B. subtilis in high density fermentation conditions, we expect that our production strains may constitute a solid basis for commercial production of 3-HP.},
 bibtype = {article},
 author = {Kalantari, Aida and Chen, Tao and Ji, Boyang and Stancik, Ivan A. and Ravikumar, Vaishnavi and Franjevic, Damjan and Saulou-Bérion, Claire and Goelzer, Anne and Mijakovic, Ivan},
 doi = {10.3389/FMICB.2017.00638/BIBTEX},
 journal = {Frontiers in Microbiology},
 number = {APR}
}

3-Hydroxypropanoic acid (3-HP) is an important biomass-derivable platform chemical that can be converted into a number of industrially relevant compounds. There have been several attempts to produce 3-HP from renewable sources in cell factories, focusing mainly on Escherichia coli, Klebsiella pneumoniae, and Saccharomyces cerevisiae. Despite the significant progress made in this field, commercially exploitable large-scale production of 3-HP in microbial strains has still not been achieved. In this study, we investigated the potential of Bacillus subtilis as a microbial platform for bioconversion of glycerol into 3-HP. Our recombinant B. subtilis strains overexpress the two-step heterologous pathway containing glycerol dehydratase and aldehyde dehydrogenase from K. pneumoniae. Genetic engineering, driven by in silico optimization, and optimization of cultivation conditions resulted in a 3-HP titer of 10 g/L, in a standard batch cultivation. Our findings provide the first report of successful introduction of the biosynthetic pathway for conversion of glycerol into 3-HP in B. subtilis. With this relatively high titer in batch, and the robustness of B. subtilis in high density fermentation conditions, we expect that our production strains may constitute a solid basis for commercial production of 3-HP.

@article{
 title = {Deficiency of essential dietary n-3 PUFA disrupts the caecal microbiome and metabolome in mice},
 type = {article},
 year = {2017},
 keywords = {Metabolomics,Microbiome,Microbiota,SCFA,control,fatty acid methyl esters,n-3 PUFA,n-3 deficient,n-3 supplemented,tricarboxylic acid},
 pages = {959-970},
 volume = {118},
 websites = {https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/deficiency-of-essential-dietary-n3-pufa-disrupts-the-caecal-microbiome-and-metabolome-in-mice/A8BCA9EB0AC0E9F67737796EF5FAA871},
 month = {12},
 publisher = {Cambridge University Press},
 day = {14},
 id = {83d93928-2fc2-382b-a7c1-46ed8025c7c9},
 created = {2025-07-07T13:25:14.173Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:01.369Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {n-3 PUFA are lipids that play crucial roles in immune-regulation, cardio-protection and neurodevelopment. However, little is known about the role that these essential dietary fats play in modulating caecal microbiota composition and the subsequent production of functional metabolites. To investigate this, female C57BL/6 mice were assigned to one of three diets (control (CON), n-3 supplemented (n3+) or n-3 deficient (n3−)) during gestation, following which their male offspring were continued on the same diets for 12 weeks. Caecal content of mothers and offspring were collected for 16S sequencing and metabolic phenotyping. n3− male offspring displayed significantly less % fat mass than n3+ and CON. n-3 Status also induced a number of changes to gut microbiota composition such that n3− offspring had greater abundance of Tenericutes, Anaeroplasma and Coriobacteriaceae. Metabolomics analysis revealed an increase in caecal metabolites involved in energy metabolism in n3+ including α-ketoglutaric acid, malic acid and fumaric acid. n3− animals displayed significantly reduced acetate, butyrate and total caecal SCFA production. These results demonstrate that dietary n-3 PUFA regulate gut microbiota homoeostasis whereby n-3 deficiency may induce a state of disturbance. Further studies are warranted to examine whether these microbial and metabolic disturbances are causally related to changes in metabolic health outcomes.},
 bibtype = {article},
 author = {Robertson, Ruairi C. and Seira Oriach, Clara and Murphy, Kiera and Moloney, Gerard M. and Cryan, John F. and Dinan, Timothy G. and Ross, R. P. and Stanton, Catherine},
 doi = {10.1017/S0007114517002999},
 journal = {British Journal of Nutrition},
 number = {11}
}

n-3 PUFA are lipids that play crucial roles in immune-regulation, cardio-protection and neurodevelopment. However, little is known about the role that these essential dietary fats play in modulating caecal microbiota composition and the subsequent production of functional metabolites. To investigate this, female C57BL/6 mice were assigned to one of three diets (control (CON), n-3 supplemented (n3+) or n-3 deficient (n3−)) during gestation, following which their male offspring were continued on the same diets for 12 weeks. Caecal content of mothers and offspring were collected for 16S sequencing and metabolic phenotyping. n3− male offspring displayed significantly less % fat mass than n3+ and CON. n-3 Status also induced a number of changes to gut microbiota composition such that n3− offspring had greater abundance of Tenericutes, Anaeroplasma and Coriobacteriaceae. Metabolomics analysis revealed an increase in caecal metabolites involved in energy metabolism in n3+ including α-ketoglutaric acid, malic acid and fumaric acid. n3− animals displayed significantly reduced acetate, butyrate and total caecal SCFA production. These results demonstrate that dietary n-3 PUFA regulate gut microbiota homoeostasis whereby n-3 deficiency may induce a state of disturbance. Further studies are warranted to examine whether these microbial and metabolic disturbances are causally related to changes in metabolic health outcomes.

@article{
 title = {Gas chromatography – mass spectrometry data processing made easy},
 type = {article},
 year = {2017},
 keywords = {Chromatography,Data processing,Deconvolution,GC–MS,PARAFAC2},
 pages = {57-64},
 volume = {1503},
 month = {6},
 publisher = {Elsevier},
 day = {23},
 id = {77be4b3a-0bd0-3123-b2c9-a2a2d3a7e8c6},
 created = {2025-07-07T13:25:14.495Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:01.697Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Evaluation of GC–MS data may be challenging due to the high complexity of data including overlapped, embedded, retention time shifted and low S/N ratio peaks. In this work, we demonstrate a new approach, PARAFAC2 based Deconvolution and Identification System (PARADISe), for processing raw GC–MS data. PARADISe is a computer platform independent freely available software incorporating a number of newly developed algorithms in a coherent framework. It offers a solution for analysts dealing with complex chromatographic data. It allows extraction of chemical/metabolite information directly from the raw data. Using PARADISe requires only few inputs from the analyst to process GC–MS data and subsequently converts raw netCDF data files into a compiled peak table. Furthermore, the method is generally robust towards minor variations in the input parameters. The method automatically performs peak identification based on deconvoluted mass spectra using integrated NIST search engine and generates an identification report. In this paper, we compare PARADISe with AMDIS and ChromaTOF in terms of peak quantification and show that PARADISe is more robust to user-defined settings and that these are easier (and much fewer) to set. PARADISe is based on non-proprietary scientifically evaluated approaches and we here show that PARADISe can handle more overlapping signals, lower signal-to-noise peaks and do so in a manner that requires only about an hours worth of work regardless of the number of samples. We also show that there are no non-detects in PARADISe, meaning that all compounds are detected in all samples.},
 bibtype = {article},
 author = {Johnsen, Lea G. and Skou, Peter B. and Khakimov, Bekzod and Bro, Rasmus},
 doi = {10.1016/J.CHROMA.2017.04.052},
 journal = {Journal of Chromatography A}
}

Evaluation of GC–MS data may be challenging due to the high complexity of data including overlapped, embedded, retention time shifted and low S/N ratio peaks. In this work, we demonstrate a new approach, PARAFAC2 based Deconvolution and Identification System (PARADISe), for processing raw GC–MS data. PARADISe is a computer platform independent freely available software incorporating a number of newly developed algorithms in a coherent framework. It offers a solution for analysts dealing with complex chromatographic data. It allows extraction of chemical/metabolite information directly from the raw data. Using PARADISe requires only few inputs from the analyst to process GC–MS data and subsequently converts raw netCDF data files into a compiled peak table. Furthermore, the method is generally robust towards minor variations in the input parameters. The method automatically performs peak identification based on deconvoluted mass spectra using integrated NIST search engine and generates an identification report. In this paper, we compare PARADISe with AMDIS and ChromaTOF in terms of peak quantification and show that PARADISe is more robust to user-defined settings and that these are easier (and much fewer) to set. PARADISe is based on non-proprietary scientifically evaluated approaches and we here show that PARADISe can handle more overlapping signals, lower signal-to-noise peaks and do so in a manner that requires only about an hours worth of work regardless of the number of samples. We also show that there are no non-detects in PARADISe, meaning that all compounds are detected in all samples.

@article{
 title = {High intake of dairy during energy restriction does not affect energy balance or the intestinal microflora compared to low dairy intake in overweight individuals in a Randomized Controlled Trial},
 type = {article},
 year = {2017},
 keywords = {au cours de la,augmentation de l,body weight,calcium,calcium pourrait accélérer la,cette étude a pour,dairy,de graisse par,energy restriction,excrétion des graisses dans,l,les matières fécales,microbiota,objectif premier de vérifier,perte de poids,perte de poids et,plan des,produits laitiers sur le,résumé,si un régime,un apport journalier en,un régime pauvre en},
 pages = {apnm-2017-0234},
 volume = {10},
 websites = {http://www.nrcresearchpress.com/doi/10.1139/apnm-2017-0234},
 id = {93417085-e62b-3ff2-8a7f-d499e3c26660},
 created = {2025-07-07T13:25:14.820Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:02.027Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {During weight loss, dairy calcium is proposed to accelerate weight and fat mass loss through increased fecal fat excretion. The primary objective was to investigate if a high-dairy energy-restricted diet is superior to low-dairy in terms of changes in body weight, body composition and fecal fat excretion over 24 weeks. Secondary objectives included fecal energy and calcium excretion, resting energy expenditure, blood pressure, lipid metabolism and gut microbiota. In a randomized, parallel-arm intervention study 11 men and 69 women (BMI 30.60.3 kg/m2, age 441 years) were allocated to a 500 kcal (2100 kJ) deficit diet either high (HD: 1500 mg calcium/d) or low (LD: 600 mg calcium/d) in dairy products for 24 weeks. Habitual calcium intake was ~1000 mg/d. Body weight loss (HD: -6.6+/-1.3 kg, LD: -7.9+/-1.5 kg, P=0.73), fat mass loss (HD: -7.8+/-1.3 %, LD: -8.5+/-1.1 %, P=0.76), changes in fecal fat excretion (HD: -0.57+/-0.76 g, LD: 0.46+/-0.70 g, P=0.12) and microbiota composition were similar for the groups over 24 weeks. However, total fat mass loss was positively associated with relative abundance of <i></i>Papillibacter <i></i>(P=0.017) independent of diet group. Consumption of a high dairy diet did not increase fecal fat or accelerate weight and fat mass loss beyond energy restriction over 24 weeks in overweight and obese adults with a habitual calcium intake of ~1000 mg/d. However, this study indicate that <i>Papillibacter</i> is involved in body compositional changes.},
 bibtype = {article},
 author = {Bendtsen, Line Quist and Blædel, Trine and Holm, Jacob Bak and Lorenzen, Janne Kunchel and Mark, Alicja Budek and Kiilerich, Pia and Kristiansen, Karsten and Astrup, Arne and Larsen, Lesli Hingstrup},
 doi = {10.1139/apnm-2017-0234},
 journal = {Applied Physiology, Nutrition, and Metabolism},
 number = {August}
}

During weight loss, dairy calcium is proposed to accelerate weight and fat mass loss through increased fecal fat excretion. The primary objective was to investigate if a high-dairy energy-restricted diet is superior to low-dairy in terms of changes in body weight, body composition and fecal fat excretion over 24 weeks. Secondary objectives included fecal energy and calcium excretion, resting energy expenditure, blood pressure, lipid metabolism and gut microbiota. In a randomized, parallel-arm intervention study 11 men and 69 women (BMI 30.60.3 kg/m2, age 441 years) were allocated to a 500 kcal (2100 kJ) deficit diet either high (HD: 1500 mg calcium/d) or low (LD: 600 mg calcium/d) in dairy products for 24 weeks. Habitual calcium intake was ~1000 mg/d. Body weight loss (HD: -6.6+/-1.3 kg, LD: -7.9+/-1.5 kg, P=0.73), fat mass loss (HD: -7.8+/-1.3 %, LD: -8.5+/-1.1 %, P=0.76), changes in fecal fat excretion (HD: -0.57+/-0.76 g, LD: 0.46+/-0.70 g, P=0.12) and microbiota composition were similar for the groups over 24 weeks. However, total fat mass loss was positively associated with relative abundance of Papillibacter (P=0.017) independent of diet group. Consumption of a high dairy diet did not increase fecal fat or accelerate weight and fat mass loss beyond energy restriction over 24 weeks in overweight and obese adults with a habitual calcium intake of ~1000 mg/d. However, this study indicate that Papillibacter is involved in body compositional changes.

@article{
 title = {Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour.},
 type = {article},
 year = {2017},
 pages = {145-152},
 volume = {154},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/28559473},
 month = {8},
 id = {ac2134b5-5b00-33f3-a6e0-2942cde8b9cb},
 created = {2025-07-07T13:25:15.200Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:02.371Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDN-POA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women.},
 bibtype = {article},
 author = {Hay-Schmidt, Anders and Finkielman, Olivia T Ejlstrup and Jensen, Benjamin A H and Høgsbro, Christine F and Bak Holm, Jacob and Johansen, Kristoffer Haurum and Jensen, Tina Kold and Andrade, Anderson Martino and Swan, Shanna H and Bornehag, Carl-gustaf and Brunak, Søren and Jegou, Bernard and Kristiansen, Karsten and Kristensen, David Møbjerg},
 doi = {10.1530/REP-17-0165},
 journal = {Reproduction (Cambridge, England)},
 number = {2}
}

Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDN-POA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women.

@article{
 title = {Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat},
 type = {article},
 year = {2017},
 keywords = {Aging,Glucose regulation,Gut microbiota,High-fat diet,Inflammation,Insulin resistance,Obesity,aging,glucose regulation,gut microbiota,high-fat diet,inflammation,insulin resistance,obesity},
 pages = {66-76},
 volume = {54},
 websites = {http://dx.doi.org/10.1016/j.jnutbio.2017.09.026},
 publisher = {Elsevier Inc.},
 id = {062bfcc0-a75c-3e56-b2f8-de3a128b11d4},
 created = {2025-07-07T13:25:15.539Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:02.784Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Damgaard, Mads T F and Pærregaard, Simone I and Søgaard, Ida and Agerholm, Marianne and Paulson, Joseph N and Treebak, Jonas T and Sina, Christian and Holm, Jacob B and Kristiansen, Karsten and Jensen, Benjamin A H},
 doi = {10.1016/j.jnutbio.2017.09.026},
 journal = {The Journal of Nutritional Biochemistry}
}

@article{
 title = {Oscillospira and related bacteria – From metagenomic species to metabolic features},
 type = {article},
 year = {2017},
 pages = {835-841},
 volume = {19},
 month = {3},
 publisher = {Blackwell Publishing Ltd},
 day = {1},
 id = {73816e5f-a153-35ab-8855-a284985447c4},
 created = {2025-10-30T12:09:26.854Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:26.854Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Oscillospira is an under-studied anaerobic bacterial genus from Clostridial cluster IV that has resisted cultivation for over a century since the first time it was observed. In recent years its 16S rRNA gene was identified in several human gut microbiota studies where it was often associated with interesting traits, especially leanness. However, very little is known about its metabolism or physiology. Here we used nearly complete genomes derived from shot-gun metagenomic data from the human gut to analyze Oscillospira and related bacteria. We used sequence similarity, gene neighbourhood information and manual metabolic pathway curation to decipher key metabolic features of this intriguing bacterial genus. We infer that Oscillospira species are butyrate producers, and at least some of them have the ability to utilize glucuronate, a common animal-derived sugar that is both produced by the human host and consumed by that host in diets rich in animal products. These findings could help explain diet-related inter-individual variation in faecal Oscillospira levels as well as the observation that the presence of this genus is reduced in diseases that involve inflammation.},
 bibtype = {article},
 author = {Gophna, Uri and Konikoff, Tom and Nielsen, Henrik Bjørn},
 doi = {10.1111/1462-2920.13658},
 journal = {Environmental Microbiology},
 number = {3}
}

Oscillospira is an under-studied anaerobic bacterial genus from Clostridial cluster IV that has resisted cultivation for over a century since the first time it was observed. In recent years its 16S rRNA gene was identified in several human gut microbiota studies where it was often associated with interesting traits, especially leanness. However, very little is known about its metabolism or physiology. Here we used nearly complete genomes derived from shot-gun metagenomic data from the human gut to analyze Oscillospira and related bacteria. We used sequence similarity, gene neighbourhood information and manual metabolic pathway curation to decipher key metabolic features of this intriguing bacterial genus. We infer that Oscillospira species are butyrate producers, and at least some of them have the ability to utilize glucuronate, a common animal-derived sugar that is both produced by the human host and consumed by that host in diets rich in animal products. These findings could help explain diet-related inter-individual variation in faecal Oscillospira levels as well as the observation that the presence of this genus is reduced in diseases that involve inflammation.

@article{
 title = {Fecal Microbiota Transplantation in Patients With Blood Disorders Inhibits Gut Colonization With Antibiotic-Resistant Bacteria: Results of a Prospective, Single-Center Study},
 type = {article},
 year = {2017},
 keywords = {antibiotic-resistant bacteria,fecal microbiota transplantation,gut colonization,hematology,infection},
 pages = {364-370},
 volume = {65},
 month = {8},
 publisher = {Oxford University Press},
 day = {1},
 id = {09b47d04-f868-3e1d-9f6e-a0114bf1d1c2},
 created = {2025-10-30T12:09:26.855Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:36.779Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background. Patients with blood disorders colonized with antibiotic-resistant bacteria (ARB) are prone to systemic infections that are difficult to treat. Reintroduction of commensal bacteria in a murine model of enterococcal colonization of the gut can lead to eradication of enterococci. We hypothesized that fecal microbiota transplantation (FMT) could be used to eradicate ARB in humans. Methods. Participants colonized with ARB were treated with intraduodenal FMT according to a prospective protocol (NCT02461199). The primary endpoint was complete ARB decolonization at 1 month after FMT. Secondary endpoints included safety assessment and partial ARB decolonization. Microbiome sequencing was performed to investigate the influence of microbial composition of the transplanted material on the outcome of FMT. Results. Twenty-five FMTs were performed in 20 participants (including 40% who had neutropenia) who were colonized by a median of 2 (range, 1-4) strains of ARB. The primary endpoint was reached in 15/25 (60%) of the FMTs and more frequently in cases in which there was no periprocedural use of antibiotics (79% vs 36%, P <.05). Among participants, 15/20 (75%) experienced complete ARB decolonization. There were no severe adverse events, and partial ARB decolonization was observed in 20/25 (80%) of the FMTs. The microbiota composition analysis revealed higher abundance of Barnesiella spp., Bacteroides, and Butyricimonas and greater bacterial richness in the fecal material, resulting in eradication of Klebsiella pneumoniae compared with nonresponders. Conclusions. FMT in patients with blood disorders is safe and promotes eradication of ARB from the gastrointestinal tract.},
 bibtype = {article},
 author = {Bilinski, Jaroslaw and Grzesiowski, Pawel and Sorensen, Nikolaj and Madry, Krzysztof and Muszynski, Jacek and Robak, Katarzyna and Wroblewska, Marta and Dzieciatkowski, Tomasz and Dulny, Grazyna and Dwilewicz-Trojaczek, Jadwiga and Wiktor-Jedrzejczak, Wieslaw and Basak, Grzegorz W.},
 doi = {10.1093/cid/cix252},
 journal = {Clinical Infectious Diseases},
 number = {3}
}

Background. Patients with blood disorders colonized with antibiotic-resistant bacteria (ARB) are prone to systemic infections that are difficult to treat. Reintroduction of commensal bacteria in a murine model of enterococcal colonization of the gut can lead to eradication of enterococci. We hypothesized that fecal microbiota transplantation (FMT) could be used to eradicate ARB in humans. Methods. Participants colonized with ARB were treated with intraduodenal FMT according to a prospective protocol (NCT02461199). The primary endpoint was complete ARB decolonization at 1 month after FMT. Secondary endpoints included safety assessment and partial ARB decolonization. Microbiome sequencing was performed to investigate the influence of microbial composition of the transplanted material on the outcome of FMT. Results. Twenty-five FMTs were performed in 20 participants (including 40% who had neutropenia) who were colonized by a median of 2 (range, 1-4) strains of ARB. The primary endpoint was reached in 15/25 (60%) of the FMTs and more frequently in cases in which there was no periprocedural use of antibiotics (79% vs 36%, P <.05). Among participants, 15/20 (75%) experienced complete ARB decolonization. There were no severe adverse events, and partial ARB decolonization was observed in 20/25 (80%) of the FMTs. The microbiota composition analysis revealed higher abundance of Barnesiella spp., Bacteroides, and Butyricimonas and greater bacterial richness in the fecal material, resulting in eradication of Klebsiella pneumoniae compared with nonresponders. Conclusions. FMT in patients with blood disorders is safe and promotes eradication of ARB from the gastrointestinal tract.

@article{
 title = {Comparative genomic analysis and characterization of incompatibility group FIB plasmid encoded virulence factors of Salmonella enterica isolated from food sources},
 type = {article},
 year = {2017},
 keywords = {Human intestinal epithelial (Caco-2) cells,Incompatibility group FIB plasmid,Iron acquisition systems (SitABCD and aerobactin),Salmonella enterica,Single nucleotide polymorphism (SNP),Virulence,Whole genome sequencing (WGS)},
 volume = {18},
 month = {8},
 publisher = {BioMed Central Ltd.},
 day = {2},
 id = {659fc52b-9b22-3ab4-8015-ee33bd666ed6},
 created = {2025-10-30T12:26:00.913Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.913Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: The degree to which the chromosomal mediated iron acquisition system contributes to virulence of many bacterial pathogens is well defined. However, the functional roles of plasmid encoded iron acquisition systems, specifically Sit and aerobactin, have yet to be determined for Salmonella spp. In a recent study, Salmonella enterica strains isolated from different food sources were sequenced on the Illumina MiSeq platform and found to harbor the incompatibility group (Inc) FIB plasmid. In this study, we examined sequence diversity and the contribution of factors encoded on the IncFIB plasmid to the virulence of S. enterica. Results: Whole genome sequences of seven S. enterica isolates were compared to genomes of serovars of S. enterica isolated from food, animal, and human sources. SeqSero analysis predicted that six strains were serovar Typhimurium and one was Heidelberg. Among the S. Typhimurium strains, single nucleotide polymorphism (SNP)-based phylogenetic analyses revealed that five of the isolates clustered as a single monophyletic S. Typhimurium subclade, while one of the other strains branched with S. Typhimurium from a bovine source. DNA sequence based phylogenetic diversity analyses showed that the IncFIB plasmid-encoded Sit and aerobactin iron acquisition systems are conserved among bacterial species including S. enterica. The IncFIB plasmid was transferred to an IncFIB plasmid deficient strain of S. enterica by conjugation. The transconjugant SE819::IncFIB persisted in human intestinal epithelial (Caco-2) cells at a higher rate than the recipient SE819. Genes of the Sit and aerobactin operons in the IncFIB plasmid were differentially expressed in iron-rich and iron-depleted growth media. Conclusions: Minimal sequence diversity was detected in the Sit and aerobactin operons in the IncFIB plasmids present among different bacterial species, including foodborne Salmonella strains. IncFIB plasmid encoded factors play a role during infection under low-iron conditions in host cells.},
 bibtype = {article},
 author = {Khajanchi, Bijay K. and Hasan, Nur A. and Choi, Seon Young and Han, Jing and Zhao, Shaohua and Colwell, Rita R. and Cerniglia, Carl E. and Foley, Steven L.},
 doi = {10.1186/S12864-017-3954-5},
 journal = {BMC Genomics},
 number = {1}
}

Background: The degree to which the chromosomal mediated iron acquisition system contributes to virulence of many bacterial pathogens is well defined. However, the functional roles of plasmid encoded iron acquisition systems, specifically Sit and aerobactin, have yet to be determined for Salmonella spp. In a recent study, Salmonella enterica strains isolated from different food sources were sequenced on the Illumina MiSeq platform and found to harbor the incompatibility group (Inc) FIB plasmid. In this study, we examined sequence diversity and the contribution of factors encoded on the IncFIB plasmid to the virulence of S. enterica. Results: Whole genome sequences of seven S. enterica isolates were compared to genomes of serovars of S. enterica isolated from food, animal, and human sources. SeqSero analysis predicted that six strains were serovar Typhimurium and one was Heidelberg. Among the S. Typhimurium strains, single nucleotide polymorphism (SNP)-based phylogenetic analyses revealed that five of the isolates clustered as a single monophyletic S. Typhimurium subclade, while one of the other strains branched with S. Typhimurium from a bovine source. DNA sequence based phylogenetic diversity analyses showed that the IncFIB plasmid-encoded Sit and aerobactin iron acquisition systems are conserved among bacterial species including S. enterica. The IncFIB plasmid was transferred to an IncFIB plasmid deficient strain of S. enterica by conjugation. The transconjugant SE819::IncFIB persisted in human intestinal epithelial (Caco-2) cells at a higher rate than the recipient SE819. Genes of the Sit and aerobactin operons in the IncFIB plasmid were differentially expressed in iron-rich and iron-depleted growth media. Conclusions: Minimal sequence diversity was detected in the Sit and aerobactin operons in the IncFIB plasmids present among different bacterial species, including foodborne Salmonella strains. IncFIB plasmid encoded factors play a role during infection under low-iron conditions in host cells.

@article{
 title = {Characterization of pathogenic Vibrio parahaemolyticus from the Chesapeake Bay, Maryland},
 type = {article},
 year = {2017},
 keywords = {Chesapeake Bay,Environment,Pathogenicity,Vibrio parahaemolyticus,Virulence},
 volume = {8},
 month = {12},
 publisher = {Frontiers Media S.A.},
 day = {15},
 id = {82548d50-f262-3a05-856f-2985b71946c2},
 created = {2025-10-30T12:26:00.963Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:13.125Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Vibrio parahaemolyticus is the leading cause of bacterial gastroenteritis associated with seafood consumption in the United States. Here we investigated the presence of virulence factors and genetic diversity of V. parahaemolyticus isolated from water, oyster, and sediment samples from the Chesapeake Bay, Maryland. Of more than 2,350 presumptive Vibrio collected, more than half were confirmed through PCR as V. parahaemolyticus, with 10 encoding both tdh and trh and 6 encoding only trh. Potentially pathogenic V. parahaemolyticus were then serotyped with O1:KUT and O3:KUT predominant. Furthermore, pulsed-field gel electrophoresis was performed and the constructed dendrogram displayed high diversity, as did results from multiple-locus VNTR analysis. Vibrio parahaemolyticus was readily isolated from Chesapeake Bay waters but was less frequently isolated from oyster and sediment samples collected during this study. Potentially pathogenic V. parahaemolyticus was isolated in fewer numbers and the isolates displayed expansive diversity. Although characteristics of the pathogenic V. parahaemolyticus were highly variable and the percent of pathogenic V. parahaemolyticus detected was low, it is important to note that, pathogenic V. parahaemolyticus are present in the Chesapeake Bay, warranting seafood monitoring to minimize risk of disease for the public, and to reduce the economic burden of V. parahaemolyticus related illness.},
 bibtype = {article},
 author = {Chen, Arlene J. and Hasan, Nur A. and Haley, Bradd J. and Taviani, Elisa and Tarnowski, Mitch and Brohawn, Kathy and Johnson, Crystal N. and Colwell, Rita R. and Huq, Anwar},
 doi = {10.3389/FMICB.2017.02460},
 journal = {Frontiers in Microbiology},
 number = {DEC}
}

Vibrio parahaemolyticus is the leading cause of bacterial gastroenteritis associated with seafood consumption in the United States. Here we investigated the presence of virulence factors and genetic diversity of V. parahaemolyticus isolated from water, oyster, and sediment samples from the Chesapeake Bay, Maryland. Of more than 2,350 presumptive Vibrio collected, more than half were confirmed through PCR as V. parahaemolyticus, with 10 encoding both tdh and trh and 6 encoding only trh. Potentially pathogenic V. parahaemolyticus were then serotyped with O1:KUT and O3:KUT predominant. Furthermore, pulsed-field gel electrophoresis was performed and the constructed dendrogram displayed high diversity, as did results from multiple-locus VNTR analysis. Vibrio parahaemolyticus was readily isolated from Chesapeake Bay waters but was less frequently isolated from oyster and sediment samples collected during this study. Potentially pathogenic V. parahaemolyticus was isolated in fewer numbers and the isolates displayed expansive diversity. Although characteristics of the pathogenic V. parahaemolyticus were highly variable and the percent of pathogenic V. parahaemolyticus detected was low, it is important to note that, pathogenic V. parahaemolyticus are present in the Chesapeake Bay, warranting seafood monitoring to minimize risk of disease for the public, and to reduce the economic burden of V. parahaemolyticus related illness.

@article{
 title = {Characterization of two cryptic plasmids isolated in Haiti from clinical Vibrio cholerae non-O1/non-O139},
 type = {article},
 year = {2017},
 keywords = {Cholera,Haiti,Non-O1/non-O139,Plasmid,Vibrio cholerae},
 volume = {8},
 month = {11},
 publisher = {Frontiers Media S.A.},
 day = {23},
 id = {cf3849b5-1db7-3f86-a70d-0ec0b324da61},
 created = {2025-10-30T12:26:00.966Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:07.113Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {We report the complete sequence of two novel plasmids, pSDH-1 and pSDH-2, isolated from clinical Vibrio cholerae non-O1/non-O139 during the early phase of the 2010 Haitian cholera epidemic. Plasmids were revealed by employing single-cell genomics and their genome content suggests self-mobilization and, for pSDH-2, a toxin-antitoxin (TA) system for plasmid stabilization was identified. The putative origin of replication of pSDH-2 was mapped suggesting it replicates following the ColE1 model of plasmid replication. pSDH-1 and pSDH-2 were widespread among environmental V. cholerae non-O1/non-O139 with variable prevalence in four Haitian Departments. pSDH-2 was the most common element, either alone or with pSDH-1. The two plasmids detection adds to the composite scenario of mobile genetic elements (MGEs) observed in V. cholerae in Haiti. The role these small cryptic plasmids circulating in Vibrio spp. play in bacterial fitness or pathogenicity merits further investigation.},
 bibtype = {article},
 author = {Ceccarelli, Daniela and Garriss, Geneviève and Choi, Seon Y. and Hasan, Nur A. and Stepanauskas, Ramunas and Pop, Mihai and Huq, Anwar and Colwell, Rita R.},
 doi = {10.3389/FMICB.2017.02283},
 journal = {Frontiers in Microbiology},
 number = {NOV}
}

We report the complete sequence of two novel plasmids, pSDH-1 and pSDH-2, isolated from clinical Vibrio cholerae non-O1/non-O139 during the early phase of the 2010 Haitian cholera epidemic. Plasmids were revealed by employing single-cell genomics and their genome content suggests self-mobilization and, for pSDH-2, a toxin-antitoxin (TA) system for plasmid stabilization was identified. The putative origin of replication of pSDH-2 was mapped suggesting it replicates following the ColE1 model of plasmid replication. pSDH-1 and pSDH-2 were widespread among environmental V. cholerae non-O1/non-O139 with variable prevalence in four Haitian Departments. pSDH-2 was the most common element, either alone or with pSDH-1. The two plasmids detection adds to the composite scenario of mobile genetic elements (MGEs) observed in V. cholerae in Haiti. The role these small cryptic plasmids circulating in Vibrio spp. play in bacterial fitness or pathogenicity merits further investigation.

@article{
 title = {Vibrio cholerae O1 with reduced susceptibility to ciprofloxacin and azithromycin isolated from a rural coastal area of Bangladesh},
 type = {article},
 year = {2017},
 keywords = {Antibiotic resistance,Azithromycin,Ciprofloxacin,El Tor,Reduced susceptibility,Vibrio cholerae},
 volume = {8},
 month = {2},
 publisher = {Frontiers Research Foundation},
 day = {21},
 id = {480cef50-785e-3e05-92d2-e1d4aaa03755},
 created = {2025-10-30T12:26:00.981Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:06.720Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Cholera outbreaks occur each year in the remote coastal areas of Bangladesh and epidemiological surveillance and routine monitoring of cholera in these areas is challenging. In this study, a total of 97 Vibrio cholerae O1 isolates from Mathbaria, Bangladesh, collected during 2010 and 2014 were analyzed for phenotypic and genotypic traits, including antimicrobial susceptibility. Of the 97 isolates, 95 possessed CTX-phage mediated genes, ctxA, ace, and zot, and two lacked the cholera toxin gene, ctxA. Also both CTX+ and CTX- V. cholerae O1 isolated in this study carried rtxC, tcpAET, and hlyA. The classical cholera toxin gene, ctxB1, was detected in 87 isolates, while eight had ctxB7. Of 95 CTX+ V. cholerae O1, 90 contained rstRET and 5 had rstRCL. All isolates, except two, contained SXT related integrase intSXT. Resistance to penicillin, streptomycin, nalidixic acid, sulfamethoxazole-trimethoprim, erythromycin, and tetracycline varied between the years of study period. Most importantly, 93% of the V. cholerae O1 were multidrug resistant. Six different resistance profiles were observed, with resistance to streptomycin, nalidixic acid, tetracycline, and sulfamethoxazole-trimethoprim predominant every year. Ciprofloxacin and azithromycin MIC were 0.003-0.75 and 0.19-2.00 μg/ml, respectively, indicating reduced susceptibility to these antibiotics. Sixteen of the V. cholerae O1 isolates showed higher MIC for azithromycin (≥ 0.5 μg/ml) and were further examined for 10 macrolide resistance genes, erm(A), erm(B), erm(C), ere(A), ere(B), mph(A), mph(B), mph(D), mef(A), and msr(A) with none testing positive for the macrolide resistance genes.},
 bibtype = {article},
 author = {Rashed, Shah M. and Hasan, Nur A. and Alam, Munirul and Sadique, Abdus and Sultana, Marzia and Hoq, Md Mozammel and Bradley Sack, R. and Colwell, Rita R. and Huq, Anwar},
 doi = {10.3389/FMICB.2017.00252},
 journal = {Frontiers in Microbiology},
 number = {FEB}
}

Cholera outbreaks occur each year in the remote coastal areas of Bangladesh and epidemiological surveillance and routine monitoring of cholera in these areas is challenging. In this study, a total of 97 Vibrio cholerae O1 isolates from Mathbaria, Bangladesh, collected during 2010 and 2014 were analyzed for phenotypic and genotypic traits, including antimicrobial susceptibility. Of the 97 isolates, 95 possessed CTX-phage mediated genes, ctxA, ace, and zot, and two lacked the cholera toxin gene, ctxA. Also both CTX+ and CTX- V. cholerae O1 isolated in this study carried rtxC, tcpAET, and hlyA. The classical cholera toxin gene, ctxB1, was detected in 87 isolates, while eight had ctxB7. Of 95 CTX+ V. cholerae O1, 90 contained rstRET and 5 had rstRCL. All isolates, except two, contained SXT related integrase intSXT. Resistance to penicillin, streptomycin, nalidixic acid, sulfamethoxazole-trimethoprim, erythromycin, and tetracycline varied between the years of study period. Most importantly, 93% of the V. cholerae O1 were multidrug resistant. Six different resistance profiles were observed, with resistance to streptomycin, nalidixic acid, tetracycline, and sulfamethoxazole-trimethoprim predominant every year. Ciprofloxacin and azithromycin MIC were 0.003-0.75 and 0.19-2.00 μg/ml, respectively, indicating reduced susceptibility to these antibiotics. Sixteen of the V. cholerae O1 isolates showed higher MIC for azithromycin (≥ 0.5 μg/ml) and were further examined for 10 macrolide resistance genes, erm(A), erm(B), erm(C), ere(A), ere(B), mph(A), mph(B), mph(D), mef(A), and msr(A) with none testing positive for the macrolide resistance genes.

@article{
 title = {SYN-004 (ribaxamase), an oral beta-lactamase, mitigates antibiotic-mediated dysbiosis in a porcine gut microbiome model},
 type = {article},
 year = {2017},
 keywords = {antibiotic,antibiotic resistance,beta-lactamase,dysbiosis,intestinal microbiology,microbiome,pig},
 pages = {66-79},
 volume = {123},
 month = {7},
 day = {1},
 id = {9a76a9a0-e6b6-3137-8f97-e4c39917c792},
 created = {2025-10-30T12:26:00.983Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.983Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Aim: To evaluate an antibiotic inactivation strategy to protect the gut microbiome from antibiotic-mediated damage. Methods and Results: SYN-004 (ribaxamase) is an orally delivered beta-lactamase intended to degrade penicillins and cephalosporins within the gastrointestinal tract to protect the microbiome. Pigs (20 kg, n = 10) were treated with ceftriaxone (CRO) (IV, 50 mg kg−1, SID) for 7 days and a cohort (n = 5) received ribaxamase (PO, 75 mg, QID) for 9 days beginning the day before antibiotic administration. Ceftriaxone serum levels were not statistically different in the antibiotic-alone and antibiotic + ribaxamase groups, indicating ribaxamase did not alter systemic antibiotic levels. Whole-genome metagenomic analyses of pig faecal DNA revealed that CRO caused significant changes to the gut microbiome and an increased frequency of antibiotic resistance genes. With ribaxamase, the gut microbiomes were not significantly different from pretreatment and antibiotic resistance gene frequency was not increased. Conclusion: Ribaxamase mitigated CRO-mediated gut microbiome dysbiosis and attenuated propagation of the antibiotic resistance genes in pigs. Significance and Impact of the Study: Damage of the microbiome can lead to overgrowth of pathogenic organisms and antibiotic exposure can promote selection for antibiotic-resistant micro-organisms. Ribaxamase has the potential to become the first therapy designed to protect the gut microbiome from antibiotic-mediated dysbiosis and reduce emergence of antibiotic resistance.},
 bibtype = {article},
 author = {Connelly, S. and Bristol, J. A. and Hubert, S. and Subramanian, P. and Hasan, N. A. and Colwell, R. R. and Kaleko, M.},
 doi = {10.1111/JAM.13432},
 journal = {Journal of Applied Microbiology},
 number = {1}
}

Aim: To evaluate an antibiotic inactivation strategy to protect the gut microbiome from antibiotic-mediated damage. Methods and Results: SYN-004 (ribaxamase) is an orally delivered beta-lactamase intended to degrade penicillins and cephalosporins within the gastrointestinal tract to protect the microbiome. Pigs (20 kg, n = 10) were treated with ceftriaxone (CRO) (IV, 50 mg kg−1, SID) for 7 days and a cohort (n = 5) received ribaxamase (PO, 75 mg, QID) for 9 days beginning the day before antibiotic administration. Ceftriaxone serum levels were not statistically different in the antibiotic-alone and antibiotic + ribaxamase groups, indicating ribaxamase did not alter systemic antibiotic levels. Whole-genome metagenomic analyses of pig faecal DNA revealed that CRO caused significant changes to the gut microbiome and an increased frequency of antibiotic resistance genes. With ribaxamase, the gut microbiomes were not significantly different from pretreatment and antibiotic resistance gene frequency was not increased. Conclusion: Ribaxamase mitigated CRO-mediated gut microbiome dysbiosis and attenuated propagation of the antibiotic resistance genes in pigs. Significance and Impact of the Study: Damage of the microbiome can lead to overgrowth of pathogenic organisms and antibiotic exposure can promote selection for antibiotic-resistant micro-organisms. Ribaxamase has the potential to become the first therapy designed to protect the gut microbiome from antibiotic-mediated dysbiosis and reduce emergence of antibiotic resistance.

@article{
 title = {Comprehensive benchmarking and ensemble approaches for metagenomic classifiers},
 type = {article},
 year = {2017},
 keywords = {Classification,Comparison,Ensemble methods,Meta-classification,Metagenomics,Pathogen detection,Shotgun sequencing,Taxonomy},
 volume = {18},
 month = {9},
 publisher = {BioMed Central Ltd.},
 day = {21},
 id = {39417d79-bed8-3078-a6de-a50a91b77268},
 created = {2025-10-30T12:26:00.987Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.987Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: One of the main challenges in metagenomics is the identification of microorganisms in clinical and environmental samples. While an extensive and heterogeneous set of computational tools is available to classify microorganisms using whole-genome shotgun sequencing data, comprehensive comparisons of these methods are limited. Results: In this study, we use the largest-to-date set of laboratory-generated and simulated controls across 846 species to evaluate the performance of 11 metagenomic classifiers. Tools were characterized on the basis of their ability to identify taxa at the genus, species, and strain levels, quantify relative abundances of taxa, and classify individual reads to the species level. Strikingly, the number of species identified by the 11 tools can differ by over three orders of magnitude on the same datasets. Various strategies can ameliorate taxonomic misclassification, including abundance filtering, ensemble approaches, and tool intersection. Nevertheless, these strategies were often insufficient to completely eliminate false positives from environmental samples, which are especially important where they concern medically relevant species. Overall, pairing tools with different classification strategies (k-mer, alignment, marker) can combine their respective advantages. Conclusions: This study provides positive and negative controls, titrated standards, and a guide for selecting tools for metagenomic analyses by comparing ranges of precision, accuracy, and recall. We show that proper experimental design and analysis parameters can reduce false positives, provide greater resolution of species in complex metagenomic samples, and improve the interpretation of results.},
 bibtype = {article},
 author = {McIntyre, Alexa B.R. and Ounit, Rachid and Afshinnekoo, Ebrahim and Prill, Robert J. and Hénaff, Elizabeth and Alexander, Noah and Minot, Samuel S. and Danko, David and Foox, Jonathan and Ahsanuddin, Sofia and Tighe, Scott and Hasan, Nur A. and Subramanian, Poorani and Moffat, Kelly and Levy, Shawn and Lonardi, Stefano and Greenfield, Nick and Colwell, Rita R. and Rosen, Gail L. and Mason, Christopher E.},
 doi = {10.1186/S13059-017-1299-7},
 journal = {Genome Biology},
 number = {1}
}

Background: One of the main challenges in metagenomics is the identification of microorganisms in clinical and environmental samples. While an extensive and heterogeneous set of computational tools is available to classify microorganisms using whole-genome shotgun sequencing data, comprehensive comparisons of these methods are limited. Results: In this study, we use the largest-to-date set of laboratory-generated and simulated controls across 846 species to evaluate the performance of 11 metagenomic classifiers. Tools were characterized on the basis of their ability to identify taxa at the genus, species, and strain levels, quantify relative abundances of taxa, and classify individual reads to the species level. Strikingly, the number of species identified by the 11 tools can differ by over three orders of magnitude on the same datasets. Various strategies can ameliorate taxonomic misclassification, including abundance filtering, ensemble approaches, and tool intersection. Nevertheless, these strategies were often insufficient to completely eliminate false positives from environmental samples, which are especially important where they concern medically relevant species. Overall, pairing tools with different classification strategies (k-mer, alignment, marker) can combine their respective advantages. Conclusions: This study provides positive and negative controls, titrated standards, and a guide for selecting tools for metagenomic analyses by comparing ranges of precision, accuracy, and recall. We show that proper experimental design and analysis parameters can reduce false positives, provide greater resolution of species in complex metagenomic samples, and improve the interpretation of results.

@article{
 title = {The microbiomes of blowflies and houseflies as bacterial transmission reservoirs},
 type = {article},
 year = {2017},
 volume = {7},
 month = {12},
 publisher = {Nature Publishing Group},
 day = {1},
 id = {ef37ea60-ae6c-309d-9f75-3e1aee99d653},
 created = {2025-10-30T12:26:00.994Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:08.967Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Blowflies and houseflies are mechanical vectors inhabiting synanthropic environments around the world. They feed and breed in fecal and decaying organic matter, but the microbiome they harbour and transport is largely uncharacterized. We sampled 116 individual houseflies and blowflies from varying habitats on three continents and subjected them to high-coverage, whole-genome shotgun sequencing. This allowed for genomic and metagenomic analyses of the host-associated microbiome at the species level. Both fly host species segregate based on principal coordinate analysis of their microbial communities, but they also show an overlapping core microbiome. Legs and wings displayed the largest microbial diversity and were shown to be an important route for microbial dispersion. The environmental sequencing approach presented here detected a stochastic distribution of human pathogens, such as Helicobacter pylori, thereby demonstrating the potential of flies as proxies for environmental and public health surveillance.},
 bibtype = {article},
 author = {Junqueira, Ana Carolina M. and Ratan, Aakrosh and Acerbi, Enzo and Drautz-Moses, Daniela I. and Premkrishnan, Balakrishnan N.V. and Costea, Paul I. and Linz, Bodo and Purbojati, Rikky W. and Paulo, Daniel F. and Gaultier, Nicolas E. and Subramanian, Poorani and Hasan, Nur A. and Colwell, Rita R. and Bork, Peer and Azeredo-Espin, Ana Maria L. and Bryant, Donald A. and Schuster, Stephan C.},
 doi = {10.1038/S41598-017-16353-X},
 journal = {Scientific Reports},
 number = {1}
}

Blowflies and houseflies are mechanical vectors inhabiting synanthropic environments around the world. They feed and breed in fecal and decaying organic matter, but the microbiome they harbour and transport is largely uncharacterized. We sampled 116 individual houseflies and blowflies from varying habitats on three continents and subjected them to high-coverage, whole-genome shotgun sequencing. This allowed for genomic and metagenomic analyses of the host-associated microbiome at the species level. Both fly host species segregate based on principal coordinate analysis of their microbial communities, but they also show an overlapping core microbiome. Legs and wings displayed the largest microbial diversity and were shown to be an important route for microbial dispersion. The environmental sequencing approach presented here detected a stochastic distribution of human pathogens, such as Helicobacter pylori, thereby demonstrating the potential of flies as proxies for environmental and public health surveillance.

@article{
 title = {Genotypic and phenotypic characterization of multidrug resistant Salmonella Typhimurium and Salmonella Kentucky strains recovered from chicken carcasses},
 type = {article},
 year = {2017},
 volume = {12},
 month = {5},
 publisher = {Public Library of Science},
 day = {1},
 id = {9ab5c911-02e5-3fa7-a024-a7cbbc358500},
 created = {2025-10-30T12:26:01.901Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:11.205Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Salmonella Typhimurium is the leading cause of human non-typhoidal gastroenteritis in the US. S. Kentucky is one the most commonly recovered serovars from commercially processed poultry carcasses. This study compared the genotypic and phenotypic properties of two Salmonella enterica strains Typhimurium (ST221-31B) and Kentucky (SK222-32B) recovered from commercially processed chicken carcasses using whole genome sequencing, phenotype characterizations and an intracellular killing assay. Illumina MiSeq platform was used for sequencing of two Salmonella genomes. Phylogenetic analysis employing homologous alignment of a 1,185 non-duplicated protein-coding gene in the Salmonella core genome demonstrated fully resolved bifurcating patterns with varying levels of diversity that separated ST221-31B and SK222-32B genomes into distinct monophyletic serovar clades. Single nucleotide polymorphism (SNP) analysis identified 2,432 (ST19) SNPs within 13 Typhimurium genomes including ST221-31B representing Sequence Type ST19 and 650 (ST152) SNPs were detected within 13 Kentucky genomes including SK222-32B representing Sequence Type ST152. In addition to serovar-specific conserved coding sequences, the genomes of ST221-31B and SK222-32B harbor several genomic regions with significant genetic differences. These included phage and phage-like elements, carbon utilization or transport operons, fimbriae operons, putative membrane associated proteinencoding genes, antibiotic resistance genes, siderophore operons, and numerous hypothetical protein-encoding genes. Phenotype microarray results demonstrated that ST221-31B is capable of utilizing certain carbon compounds more efficiently as compared to SK222-3B; namely, 1,2-propanediol, M-inositol, L-threonine, α-D-lactose, D-tagatose, adonitol, formic acid, acetoacetic acid, and L-tartaric acid. ST221-31B survived for 48 h in macrophages, while SK222-32B was mostly eliminated. Further, a 3-fold growth of ST221-31B was observed at 24 hours post-infection in chicken granulosa cells while SK222-32B was unable to replicate in these cells. These results suggest that Salmonella Typhimurium can survive host defenses better and could be more invasive than Salmonella Kentucky and provide some insights into the genomic determinants responsible for these differences.},
 bibtype = {article},
 author = {Tasmin, Rizwana and Hasan, Nur A. and Grim, Christopher J. and Grant, Ar'Quette and Choi, Seon Young and Alam, M. Samiul and Bell, Rebecca and Cavanaugh, Christopher and Balan, Kannan V. and Babu, Uma S. and Parveen, Salina},
 doi = {10.1371/JOURNAL.PONE.0176938},
 journal = {PLoS ONE},
 number = {5}
}

Salmonella Typhimurium is the leading cause of human non-typhoidal gastroenteritis in the US. S. Kentucky is one the most commonly recovered serovars from commercially processed poultry carcasses. This study compared the genotypic and phenotypic properties of two Salmonella enterica strains Typhimurium (ST221-31B) and Kentucky (SK222-32B) recovered from commercially processed chicken carcasses using whole genome sequencing, phenotype characterizations and an intracellular killing assay. Illumina MiSeq platform was used for sequencing of two Salmonella genomes. Phylogenetic analysis employing homologous alignment of a 1,185 non-duplicated protein-coding gene in the Salmonella core genome demonstrated fully resolved bifurcating patterns with varying levels of diversity that separated ST221-31B and SK222-32B genomes into distinct monophyletic serovar clades. Single nucleotide polymorphism (SNP) analysis identified 2,432 (ST19) SNPs within 13 Typhimurium genomes including ST221-31B representing Sequence Type ST19 and 650 (ST152) SNPs were detected within 13 Kentucky genomes including SK222-32B representing Sequence Type ST152. In addition to serovar-specific conserved coding sequences, the genomes of ST221-31B and SK222-32B harbor several genomic regions with significant genetic differences. These included phage and phage-like elements, carbon utilization or transport operons, fimbriae operons, putative membrane associated proteinencoding genes, antibiotic resistance genes, siderophore operons, and numerous hypothetical protein-encoding genes. Phenotype microarray results demonstrated that ST221-31B is capable of utilizing certain carbon compounds more efficiently as compared to SK222-3B; namely, 1,2-propanediol, M-inositol, L-threonine, α-D-lactose, D-tagatose, adonitol, formic acid, acetoacetic acid, and L-tartaric acid. ST221-31B survived for 48 h in macrophages, while SK222-32B was mostly eliminated. Further, a 3-fold growth of ST221-31B was observed at 24 hours post-infection in chicken granulosa cells while SK222-32B was unable to replicate in these cells. These results suggest that Salmonella Typhimurium can survive host defenses better and could be more invasive than Salmonella Kentucky and provide some insights into the genomic determinants responsible for these differences.

@article{
 title = {Gas chromatography – mass spectrometry data processing made easy},
 type = {article},
 year = {2017},
 keywords = {Chromatography,Data processing,Deconvolution,GC–MS,PARAFAC2},
 pages = {57-64},
 volume = {1503},
 month = {6},
 publisher = {Elsevier B.V.},
 day = {23},
 id = {efe2463f-560a-3abd-ab53-2f6298118b3b},
 created = {2025-10-30T12:28:33.486Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:36.181Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Evaluation of GC–MS data may be challenging due to the high complexity of data including overlapped, embedded, retention time shifted and low S/N ratio peaks. In this work, we demonstrate a new approach, PARAFAC2 based Deconvolution and Identification System (PARADISe), for processing raw GC–MS data. PARADISe is a computer platform independent freely available software incorporating a number of newly developed algorithms in a coherent framework. It offers a solution for analysts dealing with complex chromatographic data. It allows extraction of chemical/metabolite information directly from the raw data. Using PARADISe requires only few inputs from the analyst to process GC–MS data and subsequently converts raw netCDF data files into a compiled peak table. Furthermore, the method is generally robust towards minor variations in the input parameters. The method automatically performs peak identification based on deconvoluted mass spectra using integrated NIST search engine and generates an identification report. In this paper, we compare PARADISe with AMDIS and ChromaTOF in terms of peak quantification and show that PARADISe is more robust to user-defined settings and that these are easier (and much fewer) to set. PARADISe is based on non-proprietary scientifically evaluated approaches and we here show that PARADISe can handle more overlapping signals, lower signal-to-noise peaks and do so in a manner that requires only about an hours worth of work regardless of the number of samples. We also show that there are no non-detects in PARADISe, meaning that all compounds are detected in all samples.},
 bibtype = {article},
 author = {Johnsen, Lea G. and Skou, Peter B. and Khakimov, Bekzod and Bro, Rasmus},
 doi = {10.1016/j.chroma.2017.04.052},
 journal = {Journal of Chromatography A}
}

Evaluation of GC–MS data may be challenging due to the high complexity of data including overlapped, embedded, retention time shifted and low S/N ratio peaks. In this work, we demonstrate a new approach, PARAFAC2 based Deconvolution and Identification System (PARADISe), for processing raw GC–MS data. PARADISe is a computer platform independent freely available software incorporating a number of newly developed algorithms in a coherent framework. It offers a solution for analysts dealing with complex chromatographic data. It allows extraction of chemical/metabolite information directly from the raw data. Using PARADISe requires only few inputs from the analyst to process GC–MS data and subsequently converts raw netCDF data files into a compiled peak table. Furthermore, the method is generally robust towards minor variations in the input parameters. The method automatically performs peak identification based on deconvoluted mass spectra using integrated NIST search engine and generates an identification report. In this paper, we compare PARADISe with AMDIS and ChromaTOF in terms of peak quantification and show that PARADISe is more robust to user-defined settings and that these are easier (and much fewer) to set. PARADISe is based on non-proprietary scientifically evaluated approaches and we here show that PARADISe can handle more overlapping signals, lower signal-to-noise peaks and do so in a manner that requires only about an hours worth of work regardless of the number of samples. We also show that there are no non-detects in PARADISe, meaning that all compounds are detected in all samples.

@article{
 title = {Glucose metabolism via the entner-doudoroff pathway in campylobacter: A rare trait that enhances survival and promotes biofilm formation in some isolates},
 type = {article},
 year = {2016},
 keywords = {Capsule,Glycolysis,Hexose sugar,Polysaccharide,PubMLST database,Stationary-phase},
 volume = {7},
 websites = {/pmc/articles/PMC5118423/,/pmc/articles/PMC5118423/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118423/},
 month = {11},
 publisher = {Frontiers Media S.A.},
 day = {22},
 id = {d457c811-abdb-3d78-8b5a-1284c1c36321},
 created = {2025-07-07T13:25:08.154Z},
 accessed = {2024-04-11},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:55.950Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Isolates of the zoonotic pathogen Campylobacter are generally considered to be unable to metabolize glucose due to lack of key glycolytic enzymes. However, the Entner-Doudoroff (ED) pathway has been identified in Campylobacter jejuni subsp. doylei and a few C. coli isolates. A systematic search for ED pathway genes in a wide range of Campylobacter isolates and in the C. jejuni/coli PubMLST database revealed that 1.7% of > 6,000 genomes encoded a complete ED pathway, including both C. jejuni and C. coli from diverse clinical, environmental and animal sources. In rich media, glucose significantly enhanced stationary phase survival of a set of ED-positive C. coli isolates. Unexpectedly, glucose massively promoted floating biofilm formation in some of these ED-positive isolates. Metabolic profiling by gas chromatography-mass spectrometry revealed distinct responses to glucose in a low biofilm strain (CV1257) compared to a high biofilm strain (B13117), consistent with preferential diversion of hexose-6-phosphate to polysaccharide in B13117. We conclude that while the ED pathway is rare amongst Campylobacter isolates causing human disease (the majority of which would be of agricultural origin), some glucose-utilizing isolates exhibit specific fitness advantages, including stationary-phase survival and biofilm production, highlighting key physiological benefits of this pathway in addition to energy conservation.},
 bibtype = {article},
 author = {Vegge, Christina S. and Jansen van Rensburg, Melissa J. and Rasmussen, Janus J. and Maiden, Martin C.J. and Johnsen, Lea G. and Danielsen, Morten and MacIntyre, Sheila and Ingmer, Hanne and Kelly, David J.},
 doi = {10.3389/FMICB.2016.01877/FULL},
 journal = {Frontiers in Microbiology},
 number = {NOV}
}

Isolates of the zoonotic pathogen Campylobacter are generally considered to be unable to metabolize glucose due to lack of key glycolytic enzymes. However, the Entner-Doudoroff (ED) pathway has been identified in Campylobacter jejuni subsp. doylei and a few C. coli isolates. A systematic search for ED pathway genes in a wide range of Campylobacter isolates and in the C. jejuni/coli PubMLST database revealed that 1.7% of > 6,000 genomes encoded a complete ED pathway, including both C. jejuni and C. coli from diverse clinical, environmental and animal sources. In rich media, glucose significantly enhanced stationary phase survival of a set of ED-positive C. coli isolates. Unexpectedly, glucose massively promoted floating biofilm formation in some of these ED-positive isolates. Metabolic profiling by gas chromatography-mass spectrometry revealed distinct responses to glucose in a low biofilm strain (CV1257) compared to a high biofilm strain (B13117), consistent with preferential diversion of hexose-6-phosphate to polysaccharide in B13117. We conclude that while the ED pathway is rare amongst Campylobacter isolates causing human disease (the majority of which would be of agricultural origin), some glucose-utilizing isolates exhibit specific fitness advantages, including stationary-phase survival and biofilm production, highlighting key physiological benefits of this pathway in addition to energy conservation.

@article{
 title = {Removal of Polysorbate 80 by complexation prior to LC-MS analysis},
 type = {article},
 year = {2016},
 keywords = {Detergent,Liquid chromatography,Mass spectrometry,Metabolite analysis,Tween 80},
 pages = {2303-2307},
 volume = {408},
 websites = {https://link.springer.com/article/10.1007/s00216-016-9326-1},
 month = {3},
 publisher = {Springer Verlag},
 day = {1},
 id = {6ff6d04e-7dc6-3813-9f51-a17bba1d2e20},
 created = {2025-07-07T13:25:08.501Z},
 accessed = {2024-04-11},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:08.501Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The presence of Polysorbate 80 in samples can challenge liquid chromatography-electrospray ionisation mass spectrometry (LC-ESI-MS) analysis as it is easily ionised and detected. In this study, we demonstrate that interference from Polysorbate 80 can be reduced by complexation with a metal ion followed by precipitation by thiocyanate. The precipitation procedure was tested on a mixture of low molecular weight compounds (e.g. amino acids and non-amino organic acids) and it was shown that none of the tested compounds were precipitated.},
 bibtype = {article},
 author = {Jäpelt, Kristina B. and Johnsen, Lea Giørtz and Christensen, Jan H.},
 doi = {10.1007/S00216-016-9326-1/METRICS},
 journal = {Analytical and Bioanalytical Chemistry},
 number = {9}
}

The presence of Polysorbate 80 in samples can challenge liquid chromatography-electrospray ionisation mass spectrometry (LC-ESI-MS) analysis as it is easily ionised and detected. In this study, we demonstrate that interference from Polysorbate 80 can be reduced by complexation with a metal ion followed by precipitation by thiocyanate. The precipitation procedure was tested on a mixture of low molecular weight compounds (e.g. amino acids and non-amino organic acids) and it was shown that none of the tested compounds were precipitated.

@article{
 title = {A randomised, controlled, crossover study of the effect of diet on angiopoietin-like protein 4 (ANGPTL4) through modification of the gut microbiome},
 type = {article},
 year = {2016},
 keywords = {Angiopoietin-like protein 4,Gut microbiome,Lipid metabolism,Lipoprotein lipase,Obesity},
 volume = {5},
 id = {a05b09c0-d919-314a-9fa9-c63af9084014},
 created = {2025-07-07T13:25:08.854Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:56.382Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis. Animal studies have sug-gested that the ANGPTL4 protein is modulated by the gut microbiota, possibly through increased concentrations of SCFA, such as C4, found in whole-fat milk or as a result of fermentation of inulin. This study investigated whether a standardised diet either high in fat content or supplemented with inulin powder would increase plasma ANGPTL4 in overweight men and whether this increase was mediated through a compositional change of the gut micro-biota. The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies were collected after each intervention period. The study included twenty-one participants of whom eighteen completed the study. The dietary interventions did not change ANGPTL4 plasma concentration, nor was plasma ANGPTL4 associated with plasma lipids, TAG or NEFA concentration. The relative abundance of bifidobacteria following the inulin diet was higher, compared with the control diet. However, the changes in microbiota were not associated with plasma ANGPTL4 and the overall composition of the microbiota did not change between the dietary periods. Although weight was main-tained throughout the dietary periods, weight was negatively associated with plasma ANGPTL4 concentration. In the adipose tissue, ANGPTL4 expression was correlated with leptin expression, but not with hypoxia-inducible factor 1α (HIF-1α) expression.},
 bibtype = {article},
 author = {Blaedel, Trine and Holm, Jacob B and Sundekilde, Ulrik K and Schmedes, Mette S and Hess, Anne L and Lorenzen, Janne K and Kristiansen, Karsten and Dalsgaard, Trine K and Astrup, Arne and Larsen, Lesli H},
 doi = {10.1017/jns.2016.38},
 journal = {Journal of Nutritional Science},
 number = {10}
}

Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis. Animal studies have sug-gested that the ANGPTL4 protein is modulated by the gut microbiota, possibly through increased concentrations of SCFA, such as C4, found in whole-fat milk or as a result of fermentation of inulin. This study investigated whether a standardised diet either high in fat content or supplemented with inulin powder would increase plasma ANGPTL4 in overweight men and whether this increase was mediated through a compositional change of the gut micro-biota. The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies were collected after each intervention period. The study included twenty-one participants of whom eighteen completed the study. The dietary interventions did not change ANGPTL4 plasma concentration, nor was plasma ANGPTL4 associated with plasma lipids, TAG or NEFA concentration. The relative abundance of bifidobacteria following the inulin diet was higher, compared with the control diet. However, the changes in microbiota were not associated with plasma ANGPTL4 and the overall composition of the microbiota did not change between the dietary periods. Although weight was main-tained throughout the dietary periods, weight was negatively associated with plasma ANGPTL4 concentration. In the adipose tissue, ANGPTL4 expression was correlated with leptin expression, but not with hypoxia-inducible factor 1α (HIF-1α) expression.

@article{
 title = {Intrauterine exposure to paracetamol and aniline impairs female reproductive development by reducing follicle reserves and fertility.},
 type = {article},
 year = {2016},
 keywords = {2014,acetaminophen,adulthood,aiken and ozanne,aniline,development,disorders in,disruption of,follicle reserves,in males,ine environment can elevate,intrauterine exposure,much evidence points to,paracetamol,reproduction,the fact that changes,the risk of health,to the intrauter-},
 pages = {kfv332-},
 volume = {0},
 websites = {http://toxsci.oxfordjournals.org/content/early/2016/01/04/toxsci.kfv332.abstract},
 id = {c0cf4649-2565-33e7-8d2b-987e9d210e11},
 created = {2025-07-07T13:25:09.217Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:56.749Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Holm2016a},
 private_publication = {false},
 abstract = {Studies report that foetal exposure to paracetamol by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (non-pharmaceutical) sources such as metabolic conversion from the ubiquitous industrial compound aniline. In this study we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that foetal hormone signalling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Foetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum foetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life.},
 bibtype = {article},
 author = {Holm, Jacob Bak and Mazaud-Guittot, Severine and Danneskiold-Samsøe, Niels Banhos and Chalmey, Clementine and Jensen, Benjamin and Nørregård, Mette Marie and Hansen, Cecilie Hurup and Styrishave, Bjarne and Svingen, Terje and Vinggaard, Anne Marie and Koch, Holger Martin and Bowles, Josephine and Koopman, Peter and Jégou, Bernard and Kristiansen, Karsten and Kristensen, David Møbjerg},
 doi = {10.1093/toxsci/kfv332},
 journal = {Toxicological sciences : an official journal of the Society of Toxicology},
 number = {0}
}

Studies report that foetal exposure to paracetamol by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (non-pharmaceutical) sources such as metabolic conversion from the ubiquitous industrial compound aniline. In this study we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that foetal hormone signalling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Foetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum foetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life.

@article{
 title = {Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain},
 type = {article},
 year = {2016},
 websites = {http://dx.doi.org/10.1016/j.metabol.2016.09.002,http://linkinghub.elsevier.com/retrieve/pii/S0026049516301081},
 publisher = {Elsevier B.V.},
 id = {ae986e7c-49f2-3f6a-a0ff-c56cfe3764c1},
 created = {2025-07-07T13:25:09.576Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:57.126Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Jensen, Benjamin A.H. and Nielsen, Thomas S and Fritzen, Andreas M and Holm, Jacob B. and Fjære, Even and Serup, Annette K and Borkowski, Kamil and Risis, Steve and Pærregaard, Simone I and Søgaard, Ida and Poupeau, Audrey and Poulsen, Michelle and Ma, Tao and Sina, Christian and Kiens, Bente and Madsen, Lise and Kristiansen, Karsten and Treebak, Jonas T.},
 doi = {10.1016/j.metabol.2016.09.002},
 journal = {Metabolism}
}

@article{
 title = {IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis},
 type = {article},
 year = {2016},
 pages = {860-874},
 volume = {44},
 websites = {http://dx.doi.org/10.1016/j.immuni.2016.02.008},
 publisher = {Elsevier Inc.},
 id = {38ecedbc-0ec4-34e3-97c7-f6014e2bbc23},
 created = {2025-07-07T13:25:09.938Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:57.453Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Luda2016},
 private_publication = {false},
 abstract = {The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8????+ and CD4+CD8????+ T cells; the latter requiring ??8 integrin expression by migratory IRF8 dependent CD103+CD11b- DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis.},
 bibtype = {article},
 author = {Luda, Katarzyna M. and Joeris, Thorsten and Persson, Emma K. and Rivollier, Aymeric and Demiri, Mimoza and Sitnik, Katarzyna M. and Pool, Lieneke and Holm, Jacob B. and Melo-Gonzalez, Felipe and Richter, Lisa and Lambrecht, Bart N. and Kristiansen, Karsten and Travis, Mark A. and Svensson-Frej, Marcus and Kotarsky, Knut and Agace, William W.},
 doi = {10.1016/j.immuni.2016.02.008},
 journal = {Immunity},
 number = {4}
}

The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8????+ and CD4+CD8????+ T cells; the latter requiring ??8 integrin expression by migratory IRF8 dependent CD103+CD11b- DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis.

@article{
 title = {Acute infection with the intestinal parasite Trichuris muris has long-term consequences on mucosal mast cell homeostasis and epithelial integrity.},
 type = {article},
 year = {2016},
 keywords = {Acute parasite infection,Large-intestinal epithelium,MCPt-1,Mucosal mast cell,Trichuris muris},
 pages = {1-12},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/27891580},
 month = {11},
 day = {28},
 id = {5b1e3a63-6cde-3288-a430-e54e6c666142},
 created = {2025-07-07T13:25:10.300Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:57.781Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {A hallmark of parasite infection is the accumulation of innate immune cells, notably granulocytes and mast cells, at the site of infection. While this is typically viewed as a transient response, with the tissue returning to steady state once the infection is cleared, we found that mast cells accumulated in the large-intestinal epithelium following infection with the nematode Trichuris muris and persisted at this site for several months after worm expulsion. Mast cell accumulation in the epithelium was associated with the induction of type-2 immunity and appeared to be driven by increased maturation of local progenitors in the intestinal lamina propria. Furthermore, we also detected increased local and systemic levels of the mucosal mast cell protease MCPt-1, which correlated highly with the persistent epithelial mast cell population. Finally, the mast cells appeared to have striking consequences on epithelial barrier integrity, by regulation of gut permeability long after worm expulsion. These findings highlight the importance of mast cells not only in the early phases of infection but also at later stages, which has functional implications on the mucosal tissue.},
 bibtype = {article},
 author = {Sorobetea, Daniel and Holm, Jacob Bak and Henningsson, Henrietta and Kristiansen, Karsten and Svensson-Frej, Marcus},
 doi = {10.1002/eji.201646738},
 journal = {European journal of immunology}
}

A hallmark of parasite infection is the accumulation of innate immune cells, notably granulocytes and mast cells, at the site of infection. While this is typically viewed as a transient response, with the tissue returning to steady state once the infection is cleared, we found that mast cells accumulated in the large-intestinal epithelium following infection with the nematode Trichuris muris and persisted at this site for several months after worm expulsion. Mast cell accumulation in the epithelium was associated with the induction of type-2 immunity and appeared to be driven by increased maturation of local progenitors in the intestinal lamina propria. Furthermore, we also detected increased local and systemic levels of the mucosal mast cell protease MCPt-1, which correlated highly with the persistent epithelial mast cell population. Finally, the mast cells appeared to have striking consequences on epithelial barrier integrity, by regulation of gut permeability long after worm expulsion. These findings highlight the importance of mast cells not only in the early phases of infection but also at later stages, which has functional implications on the mucosal tissue.

@article{
 title = {The protein source determines the potential of high protein diets to attenuate obesity development in C57BL/6J mice.},
 type = {article},
 year = {2016},
 keywords = {adiposity,animal models,brown adipose tissue,diet,protein sources},
 pages = {196-211},
 volume = {5},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/27386160,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4916867},
 id = {dd6a1284-db2a-3478-846e-cbc84653ca26},
 created = {2025-07-07T13:25:10.663Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:58.161Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Liisberg2016},
 private_publication = {false},
 abstract = {The notion that the obesogenic potential of high fat diets in rodents is attenuated when the protein:carbohydrate ratio is increased is largely based on studies using casein or whey as the protein source. We fed C57BL/6J mice high fat-high protein diets using casein, soy, cod, beef, chicken or pork as protein sources. Casein stood out as the most efficient in preventing weight gain and accretion of adipose mass. By contrast, mice fed diets based on pork or chicken, and to a lesser extent mice fed cod or beef protein, had increased adipose tissue mass gain relative to casein fed mice. Decreasing the protein:carbohydrate ratio in diets with casein or pork as protein sources led to accentuated fat mass accumulation. Pork fed mice were more obese than casein fed mice, and relative to casein, the pork-based feed induced substantial accumulation of fat in classic interscapular brown adipose tissue accompanied by decreased UCP1 expression. Furthermore, intake of a low fat diet with casein, but not pork, as a protein source reversed diet-induced obesity. Compared to pork, casein seems unique in maintaining the classical brown morphology in interscapular brown adipose tissue with high UCP1 expression. This was accompanied by increased expression of genes involved in a futile cycling of fatty acids. Our results demonstrate that intake of high protein diets based on other protein sources may not have similar effects, and hence, the obesity protective effect of high protein diets is clearly modulated by protein source.},
 bibtype = {article},
 author = {Liisberg, Ulrike and Myrmel, Lene Secher and Fjære, Even and Rønnevik, Alexander K and Bjelland, Susanne and Fauske, Kristin Røen and Holm, Jacob Bak and Basse, Astrid Linde and Hansen, Jacob B and Liaset, Bjørn and Kristiansen, Karsten and Madsen, Lise},
 doi = {10.1080/21623945.2015.1122855},
 journal = {Adipocyte},
 number = {2}
}

The notion that the obesogenic potential of high fat diets in rodents is attenuated when the protein:carbohydrate ratio is increased is largely based on studies using casein or whey as the protein source. We fed C57BL/6J mice high fat-high protein diets using casein, soy, cod, beef, chicken or pork as protein sources. Casein stood out as the most efficient in preventing weight gain and accretion of adipose mass. By contrast, mice fed diets based on pork or chicken, and to a lesser extent mice fed cod or beef protein, had increased adipose tissue mass gain relative to casein fed mice. Decreasing the protein:carbohydrate ratio in diets with casein or pork as protein sources led to accentuated fat mass accumulation. Pork fed mice were more obese than casein fed mice, and relative to casein, the pork-based feed induced substantial accumulation of fat in classic interscapular brown adipose tissue accompanied by decreased UCP1 expression. Furthermore, intake of a low fat diet with casein, but not pork, as a protein source reversed diet-induced obesity. Compared to pork, casein seems unique in maintaining the classical brown morphology in interscapular brown adipose tissue with high UCP1 expression. This was accompanied by increased expression of genes involved in a futile cycling of fatty acids. Our results demonstrate that intake of high protein diets based on other protein sources may not have similar effects, and hence, the obesity protective effect of high protein diets is clearly modulated by protein source.

@article{
 title = {Capturing one of the human gut microbiome's most wanted: Reconstructing the genome of a novel butyrate-producing, clostridial scavenger from metagenomic sequence data},
 type = {article},
 year = {2016},
 keywords = {Binning,Butyricicoccus,Genome assembly,Metagenomics,Microbiome},
 pages = {1-13},
 volume = {7},
 id = {01f62de9-eb21-340f-9188-c9cb6e74b370},
 created = {2025-07-07T13:25:11.075Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:58.527Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Jeraldo2016},
 private_publication = {false},
 abstract = {The role of the microbiome in health and disease is attracting great attention, yet we still know little about some of the most prevalent microorganisms inside our bodies. Several years ago, Human Microbiome Project (HMP) researchers generated a list of "most wanted" taxa: bacteria both prevalent among healthy volunteers and distantly related to any sequenced organisms. Unfortunately, the challenge of assembling high-quality genomes from a tangle of metagenomic reads has slowed progress in learning about these uncultured bacteria. Here, we describe how recent advances in sequencing and analysis allowed us to assemble "most wanted" genomes from metagenomic data collected from four stool samples. Using a combination of both de novo and guided assembly methods, we assembled and binned over 100 genomes from an initial data set of over 1,300 Gbp. One of these genome bins, which met HMP's criteria for a "most wanted" taxa, contained three essentially complete genomes belonging to a previously uncultivated species. This species is most closely related to Eubacterium desmolans and the clostridial cluster IV/Clostridium leptum subgroup species Butyricicoccus pullicaecorum (71-76% average nucleotide identity). Gene function analysis indicates that the species is an obligate anaerobe, forms spores, and produces the anti-inflammatory short-chain fatty acids acetate and butyrate. It also appears to take up metabolically costly molecules such as cobalamin, methionine, and branch-chained amino acids from the environment, and to lack virulence genes. Thus, the evidence is consistent with a secondary degrader that occupies a host-dependent, nutrient-scavenging niche within the gut; its ability to produce butyrate, which is thought to play an anti-inflammatory role, makes it intriguing for the study of diseases such as colon cancer and inflammatory bowel disease. In conclusion, we have assembled essentially complete genomes from stool metagenomic data, yielding valuable information about uncultured organisms' metabolic and ecologic niches, factors that may be required to successfully culture these bacteria, and their role in maintaining health and causing disease.},
 bibtype = {article},
 author = {Jeraldo, Patricio and Hernandez, Alvaro and Nielsen, Henrik B. and Chen, Xianfeng and White, Bryan A. and Goldenfeld, Nigel and Nelson, Heidi and Alhquist, David and Boardman, Lisa and Chia, Nicholas},
 doi = {10.3389/fmicb.2016.00783},
 journal = {Frontiers in Microbiology},
 number = {MAY}
}

The role of the microbiome in health and disease is attracting great attention, yet we still know little about some of the most prevalent microorganisms inside our bodies. Several years ago, Human Microbiome Project (HMP) researchers generated a list of "most wanted" taxa: bacteria both prevalent among healthy volunteers and distantly related to any sequenced organisms. Unfortunately, the challenge of assembling high-quality genomes from a tangle of metagenomic reads has slowed progress in learning about these uncultured bacteria. Here, we describe how recent advances in sequencing and analysis allowed us to assemble "most wanted" genomes from metagenomic data collected from four stool samples. Using a combination of both de novo and guided assembly methods, we assembled and binned over 100 genomes from an initial data set of over 1,300 Gbp. One of these genome bins, which met HMP's criteria for a "most wanted" taxa, contained three essentially complete genomes belonging to a previously uncultivated species. This species is most closely related to Eubacterium desmolans and the clostridial cluster IV/Clostridium leptum subgroup species Butyricicoccus pullicaecorum (71-76% average nucleotide identity). Gene function analysis indicates that the species is an obligate anaerobe, forms spores, and produces the anti-inflammatory short-chain fatty acids acetate and butyrate. It also appears to take up metabolically costly molecules such as cobalamin, methionine, and branch-chained amino acids from the environment, and to lack virulence genes. Thus, the evidence is consistent with a secondary degrader that occupies a host-dependent, nutrient-scavenging niche within the gut; its ability to produce butyrate, which is thought to play an anti-inflammatory role, makes it intriguing for the study of diseases such as colon cancer and inflammatory bowel disease. In conclusion, we have assembled essentially complete genomes from stool metagenomic data, yielding valuable information about uncultured organisms' metabolic and ecologic niches, factors that may be required to successfully culture these bacteria, and their role in maintaining health and causing disease.

@article{
 title = {Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut},
 type = {article},
 year = {2016},
 pages = {1-9},
 volume = {1},
 websites = {http://dx.doi.org/10.1038/nmicrobiol.2016.93},
 publisher = {Nature Publishing Group},
 id = {8f66e17a-39b3-37a3-a3ff-a334c5199bc5},
 created = {2025-07-07T13:25:11.419Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:58.865Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Roager2016a},
 private_publication = {false},
 abstract = {Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transit time in humans, assessed using radio-opaque markers, is associated with overall gut microbial composition, diversity and metabolism. We find that a long colonic transit time associates with high microbial richness and is accompanied by a shift in colonic metabolism from carbohydrate fermentation to protein catabolism as reflected by higher urinary levels of potentially deleterious protein-derived metabolites. Additionally, shorter colonic transit time correlates with metabolites possibly reflecting increased renewal of the colonic mucosa. Together, this suggests that a high gut microbial richness does not per se imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies.},
 bibtype = {article},
 author = {Roager, Henrik M. and Hansen, Lea B.S. and Bahl, Martin I. and Frandsen, Henrik L. and Carvalho, Vera and Gøbel, Rikke J. and Dalgaard, Marlene D. and Plichta, Damian R. and Sparholt, Morten H. and Vestergaard, Henrik and Hansen, Torben and Sicheritz-Pontén, Thomas and Nielsen, H. Bjørn and Pedersen, Oluf and Lauritzen, Lotte and Kristensen, Mette and Gupta, Ramneek and Licht, Tine R.},
 doi = {10.1038/nmicrobiol.2016.93},
 journal = {Nature Microbiology},
 number = {9}
}

Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transit time in humans, assessed using radio-opaque markers, is associated with overall gut microbial composition, diversity and metabolism. We find that a long colonic transit time associates with high microbial richness and is accompanied by a shift in colonic metabolism from carbohydrate fermentation to protein catabolism as reflected by higher urinary levels of potentially deleterious protein-derived metabolites. Additionally, shorter colonic transit time correlates with metabolites possibly reflecting increased renewal of the colonic mucosa. Together, this suggests that a high gut microbial richness does not per se imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies.

@article{
 title = {Diet-induced obesity, energy metabolism and gut microbiota in C57BL/6J mice fed Western diets based on lean seafood or lean meat mixtures},
 type = {article},
 year = {2016},
 keywords = {Dietary protein,Meat,Microbiota,Obesity,Protein source,Seafood,Western diet},
 pages = {127-136},
 volume = {31},
 websites = {http://dx.doi.org/10.1016/j.jnutbio.2015.12.017},
 publisher = {Elsevier Inc.},
 id = {f7759b65-c24c-35f7-8b69-fac66f7c8718},
 created = {2025-07-07T13:25:11.786Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:59.190Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Holm2016},
 private_publication = {false},
 abstract = {High protein diets may protect against diet-induced obesity, but little is known regarding the effects of different protein sources consumed at standard levels. We investigated how a mixture of lean seafood or lean meat in a Western background diet modulated diet-induced obesity, energy metabolism and gut microbiota. Male C57BL/6 J mice fed a Western diet (WD) containing a mixture of lean seafood (seafood WD) for 12 weeks accumulated less fat mass than mice fed a WD containing a mixture of lean meat (meat WD). Meat WD-fed mice exhibited increased fasting blood glucose, impaired glucose clearance, elevated fasting plasma insulin and increased plasma and liver lipid levels. We observed no first choice preference for either of the WDs, but over time, mice fed the seafood WD consumed less energy than mice fed the meat WD. Mice fed the seafood WD exhibited higher spontaneous locomotor activity and a lower respiratory exchange ratio (RER) than mice fed the meat WD. Thus, higher activity together with the decreased energy intake contributed to the different phenotypes observed in mice fed the seafood WD compared to mice fed the meat WD. Comparison of the gut microbiomes of mice fed the two WDs revealed significant differences in the relative abundance of operational taxonomic units (OTUs) belonging to the orders Bacteroidales and Clostridiales, with genes involved in metabolism of aromatic amino acids exhibiting higher relative abundance in the microbiomes of mice fed the seafood WD.},
 bibtype = {article},
 author = {Holm, Jacob Bak and Rønnevik, Alexander and Tastesen, Hanne Særup and Fjære, Even and Fauske, Kristin Røen and Liisberg, Ulrike and Madsen, Lise and Kristiansen, Karsten and Liaset, Bjørn},
 doi = {10.1016/j.jnutbio.2015.12.017},
 journal = {Journal of Nutritional Biochemistry}
}

High protein diets may protect against diet-induced obesity, but little is known regarding the effects of different protein sources consumed at standard levels. We investigated how a mixture of lean seafood or lean meat in a Western background diet modulated diet-induced obesity, energy metabolism and gut microbiota. Male C57BL/6 J mice fed a Western diet (WD) containing a mixture of lean seafood (seafood WD) for 12 weeks accumulated less fat mass than mice fed a WD containing a mixture of lean meat (meat WD). Meat WD-fed mice exhibited increased fasting blood glucose, impaired glucose clearance, elevated fasting plasma insulin and increased plasma and liver lipid levels. We observed no first choice preference for either of the WDs, but over time, mice fed the seafood WD consumed less energy than mice fed the meat WD. Mice fed the seafood WD exhibited higher spontaneous locomotor activity and a lower respiratory exchange ratio (RER) than mice fed the meat WD. Thus, higher activity together with the decreased energy intake contributed to the different phenotypes observed in mice fed the seafood WD compared to mice fed the meat WD. Comparison of the gut microbiomes of mice fed the two WDs revealed significant differences in the relative abundance of operational taxonomic units (OTUs) belonging to the orders Bacteroidales and Clostridiales, with genes involved in metabolism of aromatic amino acids exhibiting higher relative abundance in the microbiomes of mice fed the seafood WD.

@article{
 title = {Human gut microbes impact host serum metabolome and insulin sensitivity},
 type = {article},
 year = {2016},
 pages = {376-381},
 volume = {535},
 id = {00fa075a-2f80-3580-b77a-3bcd671ddeba},
 created = {2025-07-07T13:25:12.164Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:59.509Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Pedersen2016},
 private_publication = {false},
 abstract = {Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.},
 bibtype = {article},
 author = {Pedersen, Helle Krogh and Gudmundsdottir, Valborg and Nielsen, Henrik Bjørn and Hyotylainen, Tuulia and Nielsen, Trine and Jensen, Benjamin A.H. and Forslund, Kristoffer and Hildebrand, Falk and Prifti, Edi and Falony, Gwen and Le Chatelier, Emmanuelle and Levenez, Florence and Doré, Joel and Mattila, Ismo and Plichta, Damian R. and Pöhö, Päivi and Hellgren, Lars I. and Arumugam, Manimozhiyan and Sunagawa, Shinichi and Vieira-Silva, Sara and Jørgensen, Torben and Holm, Jacob Bak and Trošt, Kajetan and Kristiansen, Karsten and Brix, Susanne and Raes, Jeroen and Wang, Jun and Hansen, Torben and Bork, Peer and Brunak, Søren and Oresic, Matej and Ehrlich, S. Dusko and Pedersen, Oluf},
 doi = {10.1038/nature18646},
 journal = {Nature},
 number = {7612}
}

Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.

@article{
 title = {The Mouse Intestinal Bacterial Collection (miBC) provides host-specific insight into cultured diversity and functional potential of the gut microbiota},
 type = {article},
 year = {2016},
 pages = {1-15},
 volume = {1},
 websites = {http://dx.doi.org/10.1038/nmicrobiol.2016.131},
 publisher = {Nature Publishing Group},
 id = {353d05d3-aa39-3bdb-8430-352888fa2b5d},
 created = {2025-07-07T13:25:12.519Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:59.837Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Lagkouvardos2016},
 private_publication = {false},
 abstract = {Intestinal bacteria influence mammalian physiology, but many types of bacteria are still uncharacterized. Moreover, reference strains of mouse gut bacteria are not easily available, although mouse models are extensively used in medical research. These are major limitations for the investigation of intestinal microbiomes and their interactions with diet and host. It is thus important to study in detail the diversity and functions of gut microbiota members, including those colonizing the mouse intestine. To address these issues, we aimed at establishing the Mouse Intestinal Bacterial Collection (miBC), a public repository of bacterial strains and associated genomes from the mouse gut, and studied host-specificity of colonization and sequence-based relevance of the resource. The collection includes several strains representing novel species, genera and even one family. Genomic analyses showed that certain species are specific to the mouse intestine and that a minimal consortium of 18 strains covered 50-75% of the known functional potential of metagenomes. The present work will sustain future research on microbiota-host interactions in health and disease, as it will facilitate targeted colonization and molecular studies. The resource is available at www.dsmz.de/miBC.},
 bibtype = {article},
 author = {Lagkouvardos, Ilias and Pukall, Rüdiger and Abt, Birte and Foesel, Bärbel U. and Meier-Kolthoff, Jan P. and Kumar, Neeraj and Bresciani, Anne and Martínez, Inés and Just, Sarah and Ziegler, Caroline and Brugiroux, Sandrine and Garzetti, Debora and Wenning, Mareike and Bui, Thi P.N. and Wang, Jun and Hugenholtz, Floor and Plugge, Caroline M. and Peterson, Daniel A. and Hornef, Mathias W. and Baines, John F. and Smidt, Hauke and Walter, Jens and Kristiansen, Karsten and Nielsen, Henrik B. and Haller, Dirk and Overmann, Jörg and Stecher, Bärbel and Clavel, Thomas},
 doi = {10.1038/nmicrobiol.2016.131},
 journal = {Nature Microbiology},
 number = {10}
}

Intestinal bacteria influence mammalian physiology, but many types of bacteria are still uncharacterized. Moreover, reference strains of mouse gut bacteria are not easily available, although mouse models are extensively used in medical research. These are major limitations for the investigation of intestinal microbiomes and their interactions with diet and host. It is thus important to study in detail the diversity and functions of gut microbiota members, including those colonizing the mouse intestine. To address these issues, we aimed at establishing the Mouse Intestinal Bacterial Collection (miBC), a public repository of bacterial strains and associated genomes from the mouse gut, and studied host-specificity of colonization and sequence-based relevance of the resource. The collection includes several strains representing novel species, genera and even one family. Genomic analyses showed that certain species are specific to the mouse intestine and that a minimal consortium of 18 strains covered 50-75% of the known functional potential of metagenomes. The present work will sustain future research on microbiota-host interactions in health and disease, as it will facilitate targeted colonization and molecular studies. The resource is available at www.dsmz.de/miBC.

@article{
 title = {Transcriptional interactions suggest niche segregation among microorganisms in the human gut},
 type = {article},
 year = {2016},
 volume = {1},
 websites = {http://dx.doi.org/10.1038/nmicrobiol.2016.152},
 publisher = {Nature Publishing Group},
 id = {cb57817b-7e6b-3e04-a8d8-ddd3fbe49c56},
 created = {2025-07-07T13:25:12.873Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:26:00.235Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Plichta2016},
 private_publication = {false},
 abstract = {The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species 1. Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect functional and metabolic interactions between cohabiting species 2,3. To move beyond species co-occurrence networks, we systematically identified transcriptional interactions between pairs of coexisting gut microbes using metagenomics and microarray-based metatranscriptomics data from 233 stool samples from Europeans. In 102 significantly interacting species pairs, the transcriptional changes led to a reduced expression of orthologous functions between the coexisting species. Specific species-species transcriptional interactions were enriched for functions important for H2 and CO2 homeostasis, butyrate biosynthesis, ATP-binding cassette (ABC) transporters, flagella assembly and bacterial chemotaxis, as well as for the metabolism of carbohydrates, amino acids and cofactors. The analysis gives the first insight into the microbial community-wide transcriptional interactions, and suggests that the regulation of gene expression plays an important role in species adaptation to coexistence and that niche segregation takes place at the transcriptional level.},
 bibtype = {article},
 author = {Plichta, Damian Rafal and Juncker, Agnieszka Sierakowska and Bertalan, Marcelo and Rettedal, Elizabeth and Gautier, Laurent and Varela, Encarna and Manichanh, Chaysavanh and Fouqueray, Charlène and Levenez, Florence and Nielsen, Trine and Doré, Joël and MacHado, Ana Manuel Dantas and De Evgrafov, Mari Cristina Rodriguez and Hansen, Torben and Jørgensen, Torben and Bork, Peer and Guarner, Francisco and Pedersen, Oluf and Sommer, Morten O.A. and Ehrlich, S. Dusko and Sicheritz-Pontén, Thomas and Brunak, Søren and Nielsen, H. Bjørn},
 doi = {10.1038/nmicrobiol.2016.152},
 journal = {Nature Microbiology},
 number = {August}
}

The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species 1. Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect functional and metabolic interactions between cohabiting species 2,3. To move beyond species co-occurrence networks, we systematically identified transcriptional interactions between pairs of coexisting gut microbes using metagenomics and microarray-based metatranscriptomics data from 233 stool samples from Europeans. In 102 significantly interacting species pairs, the transcriptional changes led to a reduced expression of orthologous functions between the coexisting species. Specific species-species transcriptional interactions were enriched for functions important for H2 and CO2 homeostasis, butyrate biosynthesis, ATP-binding cassette (ABC) transporters, flagella assembly and bacterial chemotaxis, as well as for the metabolism of carbohydrates, amino acids and cofactors. The analysis gives the first insight into the microbial community-wide transcriptional interactions, and suggests that the regulation of gene expression plays an important role in species adaptation to coexistence and that niche segregation takes place at the transcriptional level.

@article{
 title = {Transcriptional interactions suggest niche segregation among microorganisms in the human gut},
 type = {article},
 year = {2016},
 volume = {1},
 month = {8},
 publisher = {Nature Publishing Group},
 day = {26},
 id = {fa6e61b9-e9d8-3831-91d4-6285ec2998a0},
 created = {2025-10-30T12:09:27.330Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:09:27.330Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species 1. Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect functional and metabolic interactions between cohabiting species 2,3. To move beyond species co-occurrence networks, we systematically identified transcriptional interactions between pairs of coexisting gut microbes using metagenomics and microarray-based metatranscriptomics data from 233 stool samples from Europeans. In 102 significantly interacting species pairs, the transcriptional changes led to a reduced expression of orthologous functions between the coexisting species. Specific species-species transcriptional interactions were enriched for functions important for H2 and CO2 homeostasis, butyrate biosynthesis, ATP-binding cassette (ABC) transporters, flagella assembly and bacterial chemotaxis, as well as for the metabolism of carbohydrates, amino acids and cofactors. The analysis gives the first insight into the microbial community-wide transcriptional interactions, and suggests that the regulation of gene expression plays an important role in species adaptation to coexistence and that niche segregation takes place at the transcriptional level.},
 bibtype = {article},
 author = {Plichta, Damian Rafal and Juncker, Agnieszka Sierakowska and Bertalan, Marcelo and Rettedal, Elizabeth and Gautier, Laurent and Varela, Encarna and Manichanh, Chaysavanh and Fouqueray, Charlène and Levenez, Florence and Nielsen, Trine and Doré, Joël and MacHado, Ana Manuel Dantas and De Evgrafov, Mari Cristina Rodriguez and Hansen, Torben and Jørgensen, Torben and Bork, Peer and Guarner, Francisco and Pedersen, Oluf and Sommer, Morten O.A. and Ehrlich, S. Dusko and Sicheritz-Pontén, Thomas and Brunak, Søren and Nielsen, H. Bjørn},
 doi = {10.1038/nmicrobiol.2016.152},
 journal = {Nature Microbiology}
}

The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species 1. Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect functional and metabolic interactions between cohabiting species 2,3. To move beyond species co-occurrence networks, we systematically identified transcriptional interactions between pairs of coexisting gut microbes using metagenomics and microarray-based metatranscriptomics data from 233 stool samples from Europeans. In 102 significantly interacting species pairs, the transcriptional changes led to a reduced expression of orthologous functions between the coexisting species. Specific species-species transcriptional interactions were enriched for functions important for H2 and CO2 homeostasis, butyrate biosynthesis, ATP-binding cassette (ABC) transporters, flagella assembly and bacterial chemotaxis, as well as for the metabolism of carbohydrates, amino acids and cofactors. The analysis gives the first insight into the microbial community-wide transcriptional interactions, and suggests that the regulation of gene expression plays an important role in species adaptation to coexistence and that niche segregation takes place at the transcriptional level.

@article{
 title = {Enrichment dynamics of Listeria monocytogenes and the associated microbiome from naturally contaminated ice cream linked to a listeriosis outbreak},
 type = {article},
 year = {2016},
 keywords = {16S rRNA,Buffered Listeria enrichment broth (BLEB),Co-enriching bacteria,Enrichment,FDA,Fraser broth (FB),Half-Fraser broth (HFB),ISO,Ice cream,Listeria monocytogenes,Microbiota,NGS,Next-generation sequencing,Shotgun metagenomics,USDA,University of Vermont modified broth (UVM)},
 volume = {16},
 month = {11},
 publisher = {BioMed Central Ltd.},
 day = {16},
 id = {3583f4fd-3d8c-3c1b-9e88-f370f064fdb1},
 created = {2025-10-30T12:26:00.991Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:26.087Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Microbiota that co-enrich during efforts to recover pathogens from foodborne outbreaks interfere with efficient detection and recovery. Here, dynamics of co-enriching microbiota during recovery of Listeria monocytogenes from naturally contaminated ice cream samples linked to an outbreak are described for three different initial enrichment formulations used by the Food and Drug Administration (FDA), the International Organization of Standardization (ISO), and the United States Department of Agriculture (USDA). Enrichment cultures were analyzed using DNA extraction and sequencing from samples taken every 4 h throughout 48 h of enrichment. Resphera Insight and CosmosID analysis tools were employed for high-resolution profiling of 16S rRNA amplicons and whole genome shotgun data, respectively. Results: During enrichment, other bacterial taxa were identified, including Anoxybacillus, Geobacillus, Serratia, Pseudomonas, Erwinia, and Streptococcus spp. Surprisingly, incidence of L. monocytogenes was proportionally greater at hour 0 than when tested 4, 8, and 12 h later with all three enrichment schemes. The corresponding increase in Anoxybacillus and Geobacillus spp.indicated these taxa co-enriched in competition with L. monocytogenes during early enrichment hours. L. monocytogenes became dominant after 24 h in all three enrichments. DNA sequences obtained from shotgun metagenomic data of Listeria monocytogenes at 48 h were assembled to produce a consensus draft genome which appeared to have a similar tracking utility to pure culture isolates of L. monocytogenes. Conclusions: All three methods performed equally well for enrichment of Listeria monocytogenes. The observation of potential competitive exclusion of L. mono by Anoxybacillus and Geobacillus in early enrichment hours provided novel information that may be used to further optimize enrichment formulations. Application of Resphera Insight for high-resolution analysis of 16S amplicon sequences accurately identified L. monocytogenes. Both shotgun and 16S rRNA data supported the presence of three slightly variable genomes of L. monocytogenes. Moreover, the draft assembly of a consensus genome of L. monocytogenes from shotgun metagenomic data demonstrated the potential utility of this approach to expedite trace-back of outbreak-associated strains, although further validation will be needed to confirm this utility.},
 bibtype = {article},
 author = {Ottesen, Andrea and Ramachandran, Padmini and Reed, Elizabeth and White, James R. and Hasan, Nur and Subramanian, Poorani and Ryan, Gina and Jarvis, Karen and Grim, Christopher and Daquiqan, Ninalynn and Hanes, Darcy and Allard, Marc and Colwell, Rita and Brown, Eric and Chen, Yi},
 doi = {10.1186/S12866-016-0894-1},
 journal = {BMC Microbiology},
 number = {1}
}

Background: Microbiota that co-enrich during efforts to recover pathogens from foodborne outbreaks interfere with efficient detection and recovery. Here, dynamics of co-enriching microbiota during recovery of Listeria monocytogenes from naturally contaminated ice cream samples linked to an outbreak are described for three different initial enrichment formulations used by the Food and Drug Administration (FDA), the International Organization of Standardization (ISO), and the United States Department of Agriculture (USDA). Enrichment cultures were analyzed using DNA extraction and sequencing from samples taken every 4 h throughout 48 h of enrichment. Resphera Insight and CosmosID analysis tools were employed for high-resolution profiling of 16S rRNA amplicons and whole genome shotgun data, respectively. Results: During enrichment, other bacterial taxa were identified, including Anoxybacillus, Geobacillus, Serratia, Pseudomonas, Erwinia, and Streptococcus spp. Surprisingly, incidence of L. monocytogenes was proportionally greater at hour 0 than when tested 4, 8, and 12 h later with all three enrichment schemes. The corresponding increase in Anoxybacillus and Geobacillus spp.indicated these taxa co-enriched in competition with L. monocytogenes during early enrichment hours. L. monocytogenes became dominant after 24 h in all three enrichments. DNA sequences obtained from shotgun metagenomic data of Listeria monocytogenes at 48 h were assembled to produce a consensus draft genome which appeared to have a similar tracking utility to pure culture isolates of L. monocytogenes. Conclusions: All three methods performed equally well for enrichment of Listeria monocytogenes. The observation of potential competitive exclusion of L. mono by Anoxybacillus and Geobacillus in early enrichment hours provided novel information that may be used to further optimize enrichment formulations. Application of Resphera Insight for high-resolution analysis of 16S amplicon sequences accurately identified L. monocytogenes. Both shotgun and 16S rRNA data supported the presence of three slightly variable genomes of L. monocytogenes. Moreover, the draft assembly of a consensus genome of L. monocytogenes from shotgun metagenomic data demonstrated the potential utility of this approach to expedite trace-back of outbreak-associated strains, although further validation will be needed to confirm this utility.

@article{
 title = {Phylogenetic diversity of vibrio cholerae associated with endemic cholera in Mexico from 1991 to 2008},
 type = {article},
 year = {2016},
 volume = {7},
 month = {3},
 publisher = {American Society for Microbiology},
 day = {15},
 id = {9164cbde-6b9a-385c-a548-17eeb87a5cef},
 created = {2025-10-30T12:26:01.006Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:06.125Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {An outbreak of cholera occurred in 1991 in Mexico, where it had not been reported for more than a century and is now endemic. Vibrio cholerae O1 prototype El Tor and classical strains coexist with altered El Tor strains (1991 to 1997). Nontoxigenic (CTX-) V. cholerae El Tor dominated toxigenic (CTX+) strains (2001 to 2003), but V. cholerae CTX+ variant El Tor was isolated during 2004 to 2008, outcompeting CTX- V. cholerae. Genomes of six Mexican V. cholerae O1 strains isolated during 1991 to 2008 were sequenced and compared with both contemporary and archived strains of V. cholerae. Three were CTX+ El Tor, two were CTX- El Tor, and the remaining strain was a CTX+ classical isolate. Whole-genome sequence analysis showed the six isolates belonged to five distinct phylogenetic clades. One CTX- isolate is ancestral to the 6th and 7th pandemic CTX+ V. cholerae isolates. The other CTX- isolate joined with CTX- non-O1/O139 isolates from Haiti and seroconverted O1 isolates from Brazil and Amazonia. One CTX+ isolate was phylogenetically placed with the sixth pandemic classical clade and the V. cholerae O395 classical reference strain. Two CTX+ El Tor isolates possessing intact Vibrio seventh pandemic island II (VSPII) are related to hybrid El Tor isolates from Mozambique and Bangladesh. The third CTX+ El Tor isolate contained West African-South American (WASA) recombination in VSP-II and showed relatedness to isolates from Peru and Brazil. Except for one isolate, all Mexican isolates lack SXT/R391 integrative conjugative elements (ICEs) and sensitivity to selected antibiotics, with one isolate resistant to streptomycin. No isolates were related to contemporary isolates from Asia, Africa, or Haiti, indicating phylogenetic diversity.IMPORTANCE Sequencing of genomes of V. cholerae is critical if genetic changes occurring over time in the circulating population of an area of endemicity are to be understood. Although cholera outbreaks occurred rarely in Mexico prior to the 1990s, genetically diverse V. cholerae O1 strains were isolated between 1991 and 2008. Despite the lack of strong evidence, the notion that cholera was transmitted from Africa to Latin America has been proposed in the literature. In this study, we have applied whole-genome sequence analysis to a set of 124 V. cholerae strains, including six Mexican isolates, to determine their phylogenetic relationships. Phylogenetic analysis indicated the six V. cholerae O1 isolates belong to five phylogenetic clades: i.e., basal, nontoxigenic, classical, El Tor, and hybrid El Tor. Thus, the results of phylogenetic analysis, coupled with CTX ϕ array and antibiotic susceptibility, do not support single-source transmission of cholera to Mexico from African countries. The association of indigenous populations of V. cholerae that has been observed in this study suggests it plays a significant role in the dynamics of cholera in Mexico.},
 bibtype = {article},
 author = {Choi, Seon Young and Rashed, Shah M. and Hasan, Nur A. and Alam, Munirul and Islam, Tarequl and Sadique, Abdus and Johura, Fatema Tuz and Eppinger, Mark and Ravel, Jacques and Huq, Anwar and Cravioto, Alejandro and Colwell, Rita R.},
 doi = {10.1128/MBIO.02160-15},
 journal = {mBio},
 number = {2}
}

An outbreak of cholera occurred in 1991 in Mexico, where it had not been reported for more than a century and is now endemic. Vibrio cholerae O1 prototype El Tor and classical strains coexist with altered El Tor strains (1991 to 1997). Nontoxigenic (CTX-) V. cholerae El Tor dominated toxigenic (CTX+) strains (2001 to 2003), but V. cholerae CTX+ variant El Tor was isolated during 2004 to 2008, outcompeting CTX- V. cholerae. Genomes of six Mexican V. cholerae O1 strains isolated during 1991 to 2008 were sequenced and compared with both contemporary and archived strains of V. cholerae. Three were CTX+ El Tor, two were CTX- El Tor, and the remaining strain was a CTX+ classical isolate. Whole-genome sequence analysis showed the six isolates belonged to five distinct phylogenetic clades. One CTX- isolate is ancestral to the 6th and 7th pandemic CTX+ V. cholerae isolates. The other CTX- isolate joined with CTX- non-O1/O139 isolates from Haiti and seroconverted O1 isolates from Brazil and Amazonia. One CTX+ isolate was phylogenetically placed with the sixth pandemic classical clade and the V. cholerae O395 classical reference strain. Two CTX+ El Tor isolates possessing intact Vibrio seventh pandemic island II (VSPII) are related to hybrid El Tor isolates from Mozambique and Bangladesh. The third CTX+ El Tor isolate contained West African-South American (WASA) recombination in VSP-II and showed relatedness to isolates from Peru and Brazil. Except for one isolate, all Mexican isolates lack SXT/R391 integrative conjugative elements (ICEs) and sensitivity to selected antibiotics, with one isolate resistant to streptomycin. No isolates were related to contemporary isolates from Asia, Africa, or Haiti, indicating phylogenetic diversity.IMPORTANCE Sequencing of genomes of V. cholerae is critical if genetic changes occurring over time in the circulating population of an area of endemicity are to be understood. Although cholera outbreaks occurred rarely in Mexico prior to the 1990s, genetically diverse V. cholerae O1 strains were isolated between 1991 and 2008. Despite the lack of strong evidence, the notion that cholera was transmitted from Africa to Latin America has been proposed in the literature. In this study, we have applied whole-genome sequence analysis to a set of 124 V. cholerae strains, including six Mexican isolates, to determine their phylogenetic relationships. Phylogenetic analysis indicated the six V. cholerae O1 isolates belong to five phylogenetic clades: i.e., basal, nontoxigenic, classical, El Tor, and hybrid El Tor. Thus, the results of phylogenetic analysis, coupled with CTX ϕ array and antibiotic susceptibility, do not support single-source transmission of cholera to Mexico from African countries. The association of indigenous populations of V. cholerae that has been observed in this study suggests it plays a significant role in the dynamics of cholera in Mexico.

@article{
 title = {Cross-talk among flesh-eating Aeromonas hydrophila strains in mixed infection leading to necrotizing fasciitis},
 type = {article},
 year = {2016},
 keywords = {Aeromonas hydrophila,Intramuscular mouse model,Metagenomics,Mixed infections,Necrotizing fasciitis},
 pages = {722-727},
 volume = {113},
 month = {1},
 publisher = {National Academy of Sciences},
 day = {19},
 id = {69876ff5-1061-3fd6-b504-7ecb0e95d95f},
 created = {2025-10-30T12:26:01.040Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:09.822Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Necrotizing fasciitis (NF) caused by flesh-eating bacteria is associated with high case fatality. In an earlier study, we reported infection of an immunocompetent individual with multiple strains of Aeromonas hydrophila (NF1-NF4), the latter three constituted a clonal group whereas NF1 was phylogenetically distinct. To understand the complex interactions of these strains in NF pathophysiology, a mouse model was used, whereby either single or mixed A. hydrophila strains were injected intramuscularly. NF2, which harbors exotoxin A (exoA) gene, was highly virulent when injected alone, but its virulence was attenuated in the presence of NF1 (exoA-minus). NF1 alone, although not lethal to animals, became highly virulent when combined with NF2, its virulence augmented by cis-exoA expression when injected alone in mice. Based on metagenomics and microbiological analyses, it was found that, in mixed infection, NF1 selectively disseminated to mouse peripheral organs, whereas the other strains (NF2, NF3, and NF4) were confined to the injection site and eventually cleared. In vitro studies showed NF2 to be more effectively phagocytized and killed by macrophages than NF1. NF1 inhibited growth of NF2 on solid media, but ExoA of NF2 augmented virulence of NF1 and the presence of NF1 facilitated clearance of NF2 from animals either by enhanced priming of host immune system or direct killing via a contact-dependent mechanism.},
 bibtype = {article},
 author = {Ponnusamy, Duraisamy and Kozlova, Elena V. and Sha, Jian and Erova, Tatiana E. and Azar, Sasha R. and Fitts, Eric C. and Kirtley, Michelle L. and Tiner, Bethany L. and Andersson, Jourdan A. and Grim, Christopher J. and Isom, Richard P. and Hasan, Nur A. and Colwell, Rita R. and Chopra, Ashok K.},
 doi = {10.1073/PNAS.1523817113},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 number = {3}
}

Necrotizing fasciitis (NF) caused by flesh-eating bacteria is associated with high case fatality. In an earlier study, we reported infection of an immunocompetent individual with multiple strains of Aeromonas hydrophila (NF1-NF4), the latter three constituted a clonal group whereas NF1 was phylogenetically distinct. To understand the complex interactions of these strains in NF pathophysiology, a mouse model was used, whereby either single or mixed A. hydrophila strains were injected intramuscularly. NF2, which harbors exotoxin A (exoA) gene, was highly virulent when injected alone, but its virulence was attenuated in the presence of NF1 (exoA-minus). NF1 alone, although not lethal to animals, became highly virulent when combined with NF2, its virulence augmented by cis-exoA expression when injected alone in mice. Based on metagenomics and microbiological analyses, it was found that, in mixed infection, NF1 selectively disseminated to mouse peripheral organs, whereas the other strains (NF2, NF3, and NF4) were confined to the injection site and eventually cleared. In vitro studies showed NF2 to be more effectively phagocytized and killed by macrophages than NF1. NF1 inhibited growth of NF2 on solid media, but ExoA of NF2 augmented virulence of NF1 and the presence of NF1 facilitated clearance of NF2 from animals either by enhanced priming of host immune system or direct killing via a contact-dependent mechanism.

@article{
 title = {Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection},
 type = {article},
 year = {2016},
 keywords = {Antibiotic risk factors,Beta-lactamase,Clostridium difficile,Healthcare-associated infections,Microbiome},
 pages = {58-67},
 volume = {41},
 month = {10},
 publisher = {Academic Press},
 day = {1},
 id = {ced4f73b-5c2e-32e0-88bc-5634ff4c9a1c},
 created = {2025-10-30T12:26:02.077Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:06.285Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. The ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as Clostridium difficile. A novel approach to protect the microbiome from antibiotic-mediated dysbiosis is the use of beta-lactamase enzymes to degrade residual antibiotics in the gastrointestinal tract before the microflora are harmed. Here we present the preclinical development and early clinical studies of the beta-lactamase enzymes, P3A, currently referred to as SYN-004, and its precursor, P1A. Both P1A and SYN-004 were designed as orally-delivered, non-systemically available therapeutics for use with intravenous beta-lactam antibiotics. SYN-004 was engineered from P1A, a beta-lactamase isolated from Bacillus licheniformis, to broaden its antibiotic degradation profile. SYN-004 efficiently hydrolyses penicillins and cephalosporins, the most widely used IV beta-lactam antibiotics. In animal studies, SYN-004 degraded ceftriaxone in the GI tract of dogs and protected the microbiome of pigs from ceftriaxone-induced changes. Phase I clinical studies demonstrated SYN-004 safety and tolerability. Phase 2 studies are in progress to assess the utility of SYN-004 for the prevention of antibiotic-associated diarrhea and Clostridium difficile disease.},
 bibtype = {article},
 author = {Kaleko, Michael and Bristol, J. Andrew and Hubert, Steven and Parsley, Todd and Widmer, Giovanni and Tzipori, Saul and Subramanian, Poorani and Hasan, Nur and Koski, Perrti and Kokai-Kun, John and Sliman, Joseph and Jones, Annie and Connelly, Sheila},
 doi = {10.1016/J.ANAEROBE.2016.05.015},
 journal = {Anaerobe}
}

The gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. The ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as Clostridium difficile. A novel approach to protect the microbiome from antibiotic-mediated dysbiosis is the use of beta-lactamase enzymes to degrade residual antibiotics in the gastrointestinal tract before the microflora are harmed. Here we present the preclinical development and early clinical studies of the beta-lactamase enzymes, P3A, currently referred to as SYN-004, and its precursor, P1A. Both P1A and SYN-004 were designed as orally-delivered, non-systemically available therapeutics for use with intravenous beta-lactam antibiotics. SYN-004 was engineered from P1A, a beta-lactamase isolated from Bacillus licheniformis, to broaden its antibiotic degradation profile. SYN-004 efficiently hydrolyses penicillins and cephalosporins, the most widely used IV beta-lactam antibiotics. In animal studies, SYN-004 degraded ceftriaxone in the GI tract of dogs and protected the microbiome of pigs from ceftriaxone-induced changes. Phase I clinical studies demonstrated SYN-004 safety and tolerability. Phase 2 studies are in progress to assess the utility of SYN-004 for the prevention of antibiotic-associated diarrhea and Clostridium difficile disease.

@article{
 title = {Removal of Polysorbate 80 by complexation prior to LC-MS analysis},
 type = {article},
 year = {2016},
 keywords = {Detergent,Liquid chromatography,Mass spectrometry,Metabolite analysis,Tween 80},
 pages = {2303-2307},
 volume = {408},
 month = {3},
 publisher = {Springer Verlag},
 day = {1},
 id = {891e0015-878c-3fe2-ad82-b622775bc8ff},
 created = {2025-10-30T12:28:33.455Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:28:33.455Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The presence of Polysorbate 80 in samples can challenge liquid chromatography-electrospray ionisation mass spectrometry (LC-ESI-MS) analysis as it is easily ionised and detected. In this study, we demonstrate that interference from Polysorbate 80 can be reduced by complexation with a metal ion followed by precipitation by thiocyanate. The precipitation procedure was tested on a mixture of low molecular weight compounds (e.g. amino acids and non-amino organic acids) and it was shown that none of the tested compounds were precipitated.},
 bibtype = {article},
 author = {Jäpelt, Kristina B. and Johnsen, Lea Giørtz and Christensen, Jan H.},
 doi = {10.1007/s00216-016-9326-1},
 journal = {Analytical and Bioanalytical Chemistry},
 number = {9}
}

The presence of Polysorbate 80 in samples can challenge liquid chromatography-electrospray ionisation mass spectrometry (LC-ESI-MS) analysis as it is easily ionised and detected. In this study, we demonstrate that interference from Polysorbate 80 can be reduced by complexation with a metal ion followed by precipitation by thiocyanate. The precipitation procedure was tested on a mixture of low molecular weight compounds (e.g. amino acids and non-amino organic acids) and it was shown that none of the tested compounds were precipitated.

@article{
 title = {Glucose Metabolism via the Entner-Doudoroff Pathway in Campylobacter: A Rare Trait that Enhances Survival and Promotes Biofilm Formation in Some Isolates.},
 type = {article},
 year = {2016},
 keywords = {PubMLST database,capsule,glycolysis,hexose sugar,polysaccharide,stationary-phase},
 pages = {1877},
 volume = {7},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/27920773,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5118423},
 month = {11},
 publisher = {Frontiers Media S.A.},
 day = {22},
 id = {784920a4-ab80-322d-a85f-82c7620b0f9f},
 created = {2025-10-30T12:28:34.009Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:29:57.325Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Isolates of the zoonotic pathogen Campylobacter are generally considered to be unable to metabolize glucose due to lack of key glycolytic enzymes. However, the Entner-Doudoroff (ED) pathway has been identified in Campylobacter jejuni subsp. doylei and a few C. coli isolates. A systematic search for ED pathway genes in a wide range of Campylobacter isolates and in the C. jejuni/coli PubMLST database revealed that 1.7% of >6,000 genomes encoded a complete ED pathway, including both C. jejuni and C. coli from diverse clinical, environmental and animal sources. In rich media, glucose significantly enhanced stationary phase survival of a set of ED-positive C. coli isolates. Unexpectedly, glucose massively promoted floating biofilm formation in some of these ED-positive isolates. Metabolic profiling by gas chromatography-mass spectrometry revealed distinct responses to glucose in a low biofilm strain (CV1257) compared to a high biofilm strain (B13117), consistent with preferential diversion of hexose-6-phosphate to polysaccharide in B13117. We conclude that while the ED pathway is rare amongst Campylobacter isolates causing human disease (the majority of which would be of agricultural origin), some glucose-utilizing isolates exhibit specific fitness advantages, including stationary-phase survival and biofilm production, highlighting key physiological benefits of this pathway in addition to energy conservation.},
 bibtype = {article},
 author = {Vegge, Christina S and Jansen van Rensburg, Melissa J and Rasmussen, Janus J and Maiden, Martin C J and Johnsen, Lea G and Danielsen, Morten and MacIntyre, Sheila and Ingmer, Hanne and Kelly, David J},
 doi = {10.3389/fmicb.2016.01877},
 journal = {Frontiers in microbiology},
 number = {NOV}
}

Isolates of the zoonotic pathogen Campylobacter are generally considered to be unable to metabolize glucose due to lack of key glycolytic enzymes. However, the Entner-Doudoroff (ED) pathway has been identified in Campylobacter jejuni subsp. doylei and a few C. coli isolates. A systematic search for ED pathway genes in a wide range of Campylobacter isolates and in the C. jejuni/coli PubMLST database revealed that 1.7% of >6,000 genomes encoded a complete ED pathway, including both C. jejuni and C. coli from diverse clinical, environmental and animal sources. In rich media, glucose significantly enhanced stationary phase survival of a set of ED-positive C. coli isolates. Unexpectedly, glucose massively promoted floating biofilm formation in some of these ED-positive isolates. Metabolic profiling by gas chromatography-mass spectrometry revealed distinct responses to glucose in a low biofilm strain (CV1257) compared to a high biofilm strain (B13117), consistent with preferential diversion of hexose-6-phosphate to polysaccharide in B13117. We conclude that while the ED pathway is rare amongst Campylobacter isolates causing human disease (the majority of which would be of agricultural origin), some glucose-utilizing isolates exhibit specific fitness advantages, including stationary-phase survival and biofilm production, highlighting key physiological benefits of this pathway in addition to energy conservation.

@article{
 title = {A catalog of the mouse gut metagenome},
 type = {article},
 year = {2015},
 pages = {1103-1108},
 volume = {33},
 id = {fb401f33-6e4e-3a9f-9ea0-7fdb191c12e6},
 created = {2025-07-07T13:25:06.720Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:54.555Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xiao2015},
 private_publication = {false},
 abstract = {We established a catalog of the mouse gut metagenome comprising ∼ 2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies.},
 bibtype = {article},
 author = {Xiao, Liang and Feng, Qiang and Liang, Suisha and Sonne, Si Brask and Xia, Zhongkui and Qiu, Xinmin and Li, Xiaoping and Long, Hua and Zhang, Jianfeng and Zhang, Dongya and Liu, Chuan and Fang, Zhiwei and Chou, Joyce and Glanville, Jacob and Hao, Qin and Kotowska, Dorota and Colding, Camilla and Licht, Tine Rask and Wu, Donghai and Yu, Jun and Sung, Joseph Jao Yiu and Liang, Qiaoyi and Li, Junhua and Jia, Huijue and Lan, Zhou and Tremaroli, Valentina and Dworzynski, Piotr and Nielsen, H. Bjørn and Bäckhed, Fredrik and Doré, Joël and Le Chatelier, Emmanuelle and Ehrlich, S. Dusko and Lin, John C. and Arumugam, Manimozhiyan and Wang, Jun and Madsen, Lise and Kristiansen, Karsten},
 doi = {10.1038/nbt.3353},
 journal = {Nature Biotechnology},
 number = {10}
}

We established a catalog of the mouse gut metagenome comprising ∼ 2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies.

@article{
 title = {A retrospective metagenomics approach to studying Blastocystis},
 type = {article},
 year = {2015},
 keywords = {Data mining,Eukaryote,Gut ecology,Microbiota,NGS,Parasite},
 pages = {1-9},
 volume = {91},
 id = {1373d7f5-f843-3a18-99d2-6eae87c7ea7c},
 created = {2025-07-07T13:25:07.071Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:54.948Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Andersen2015},
 private_publication = {false},
 abstract = {Blastocystis is a common single-celled intestinal parasitic genus, comprising several subtypes. Here, we screened data obtained by metagenomic analysis of faecal DNA for Blastocystis by searching for subtype-specific genes in coabundance gene groups, which are groups of genes that covary across a selection of 316 human faecal samples, hence representing genes originating from a single subtype. The 316 faecal samples were from 236 healthy individuals, 13 patients with Crohn's disease (CD) and 67 patients with ulcerative colitis (UC). The prevalence of Blastocystis was 20.3% in the healthy individuals and 14.9% in patients with UC. Meanwhile, Blastocystis was absent in patients with CD. Individuals with intestinal microbiota dominated by Bacteroides were much less prone to having Blastocystis-positive stool (Matthew's correlation coefficient = -0.25, P < 0.0001) than individuals with Ruminococcus- and Prevotella-driven enterotypes. This is the first study to investigate the relationship between Blastocystis and communities of gut bacteria using a metagenomics approach. The study serves as an example of how it is possible to retrospectively investigate microbial eukaryotic communities in the gut using metagenomic datasets targeting the bacterial component of the intestinal microbiome and the interplay between these microbial communities.},
 bibtype = {article},
 author = {Andersen, Lee O.Brien and Bonde, Ida and Nielsen, H. B.Henrik Bjørn and Stensvold, Christen Rune},
 doi = {10.1093/femsec/fiv072},
 journal = {FEMS Microbiology Ecology},
 number = {7}
}

Blastocystis is a common single-celled intestinal parasitic genus, comprising several subtypes. Here, we screened data obtained by metagenomic analysis of faecal DNA for Blastocystis by searching for subtype-specific genes in coabundance gene groups, which are groups of genes that covary across a selection of 316 human faecal samples, hence representing genes originating from a single subtype. The 316 faecal samples were from 236 healthy individuals, 13 patients with Crohn's disease (CD) and 67 patients with ulcerative colitis (UC). The prevalence of Blastocystis was 20.3% in the healthy individuals and 14.9% in patients with UC. Meanwhile, Blastocystis was absent in patients with CD. Individuals with intestinal microbiota dominated by Bacteroides were much less prone to having Blastocystis-positive stool (Matthew's correlation coefficient = -0.25, P < 0.0001) than individuals with Ruminococcus- and Prevotella-driven enterotypes. This is the first study to investigate the relationship between Blastocystis and communities of gut bacteria using a metagenomics approach. The study serves as an example of how it is possible to retrospectively investigate microbial eukaryotic communities in the gut using metagenomic datasets targeting the bacterial component of the intestinal microbiome and the interplay between these microbial communities.

@article{
 title = {Chronic Trichuris muris Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance of Lactobacilli.},
 type = {article},
 year = {2015},
 pages = {e0125495},
 volume = {10},
 websites = {http://dx.doi.org/10.1371/journal.pone.0125495},
 month = {1},
 day = {5},
 id = {37d69e91-6eff-34ba-89d2-205a9910287c},
 created = {2025-07-07T13:25:07.456Z},
 accessed = {2015-05-13},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:55.291Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Holm2015},
 private_publication = {false},
 abstract = {The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T. muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes.},
 bibtype = {article},
 author = {Holm, Jacob Bak and Sorobetea, Daniel and Kiilerich, Pia and Ramayo-Caldas, Yuliaxis and Estellé, Jordi and Ma, Tao and Madsen, Lise and Kristiansen, Karsten and Svensson-Frej, Marcus},
 doi = {10.1371/journal.pone.0125495},
 journal = {PloS one},
 number = {5}
}

The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T. muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes.

@article{
 title = {Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota},
 type = {article},
 year = {2015},
 pages = {262-266},
 volume = {528},
 websites = {http://dx.doi.org/10.1038/nature15766},
 publisher = {Nature Publishing Group},
 id = {42e3e109-8290-3871-80fe-ff4b77c3df3d},
 created = {2025-07-07T13:25:07.809Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:55.622Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 citation_key = {Forslund2015},
 private_publication = {false},
 abstract = {In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.},
 bibtype = {article},
 author = {Forslund, Kristoffer and Hildebrand, Falk and Nielsen, Trine and Falony, Gwen and Le Chatelier, Emmanuelle and Sunagawa, Shinichi and Prifti, Edi and Vieira-Silva, Sara and Gudmundsdottir, Valborg and Krogh Pedersen, Helle and Arumugam, Manimozhiyan and Kristiansen, Karsten and Yvonne Voigt, Anita and Vestergaard, Henrik and Hercog, Rajna and Igor Costea, Paul and Roat Kultima, Jens and Li, Junhua and Jørgensen, Torben and Levenez, Florence and Dore, Joël and Bjørn Nielsen, H. and Brunak, Søren and Raes, Jeroen and Hansen, Torben and Wang, Jun and Dusko Ehrlich, S. and Bork, Peer and Pedersen, Oluf},
 doi = {10.1038/nature15766},
 journal = {Nature},
 number = {7581}
}

In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.

@article{
 title = {Non-O1/Non-O139 Vibrio cholerae carrying multiple virulence factors and V. cholerae O1 in the Chesapeake Bay, Maryland},
 type = {article},
 year = {2015},
 pages = {1909-1918},
 volume = {81},
 publisher = {American Society for Microbiology},
 id = {bde61cb2-1d42-3e6c-b798-1d7f10f77505},
 created = {2025-10-30T12:26:00.907Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.907Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Non-O1/non-O139 Vibrio cholerae inhabits estuarine and coastal waters globally, but its clinical significance has not been sufficiently investigated, despite the fact that it has been associated with septicemia and gastroenteritis. The emergence of virulent non-O1/non-O139 V. cholerae is consistent with the recognition of new pathogenic variants worldwide. Oyster, sediment, and water samples were collected during a vibrio surveillance program carried out from 2009 to 2012 in the Chesapeake Bay, Maryland. V. cholerae O1 was detected by a direct fluorescent-antibody (DFA) assay but was not successfully cultured, whereas 395 isolates of non-O1/non-O139 V. cholerae were confirmed by multiplex PCR and serology. Only a few of the non-O1/non-O139 V. cholerae isolates were resistant to ampicillin and/or penicillin. Most of the isolates were sensitive to all antibiotics tested, and 77 to 90% carried the El Tor variant hemolysin gene hlyAET, the actin cross-linking repeats in toxin gene rtxA, the hemagglutinin protease gene hap, and the type 6 secretion system. About 19 to 21% of the isolates carried the neuraminidase-encoding gene nanH and/or the heat-stable toxin (NAG-ST), and only 5% contained a type 3 secretion system. None of the non-O1/non-O139 V. cholerae isolates contained Vibrio pathogenicity island-associated genes. However, ctxA, ace, or zot was present in nine isolates. Fifty-five different genotypes showed up to 12 virulence factors, independent of the source of isolation, and represent the first report of both antibiotic susceptibility and virulence associated with non-O1/non-O139 V. cholerae from the Chesapeake Bay. Since these results confirm the presence of potentially pathogenic non-O1/non-O139 V. cholerae, monitoring for total V. cholerae, regardless of serotype, should be done within the context of public health.},
 bibtype = {article},
 author = {Ceccarelli, Daniela and Chen, Arlene and Hasan, Nur A. and Rashed, Shah M. and Huq, Anwar and Colwell, Rita R.},
 doi = {10.1128/AEM.03540-14},
 journal = {Applied and Environmental Microbiology},
 number = {6}
}

Non-O1/non-O139 Vibrio cholerae inhabits estuarine and coastal waters globally, but its clinical significance has not been sufficiently investigated, despite the fact that it has been associated with septicemia and gastroenteritis. The emergence of virulent non-O1/non-O139 V. cholerae is consistent with the recognition of new pathogenic variants worldwide. Oyster, sediment, and water samples were collected during a vibrio surveillance program carried out from 2009 to 2012 in the Chesapeake Bay, Maryland. V. cholerae O1 was detected by a direct fluorescent-antibody (DFA) assay but was not successfully cultured, whereas 395 isolates of non-O1/non-O139 V. cholerae were confirmed by multiplex PCR and serology. Only a few of the non-O1/non-O139 V. cholerae isolates were resistant to ampicillin and/or penicillin. Most of the isolates were sensitive to all antibiotics tested, and 77 to 90% carried the El Tor variant hemolysin gene hlyAET, the actin cross-linking repeats in toxin gene rtxA, the hemagglutinin protease gene hap, and the type 6 secretion system. About 19 to 21% of the isolates carried the neuraminidase-encoding gene nanH and/or the heat-stable toxin (NAG-ST), and only 5% contained a type 3 secretion system. None of the non-O1/non-O139 V. cholerae isolates contained Vibrio pathogenicity island-associated genes. However, ctxA, ace, or zot was present in nine isolates. Fifty-five different genotypes showed up to 12 virulence factors, independent of the source of isolation, and represent the first report of both antibiotic susceptibility and virulence associated with non-O1/non-O139 V. cholerae from the Chesapeake Bay. Since these results confirm the presence of potentially pathogenic non-O1/non-O139 V. cholerae, monitoring for total V. cholerae, regardless of serotype, should be done within the context of public health.

@article{
 title = {Concordance and discordance of sequence survey methods for molecular epidemiology},
 type = {article},
 year = {2015},
 keywords = {Biological weapons,Bioterrorism,Data type,Genomes,High-throughput sequencing,MLST,Molecular epidemiology,Phylogenomics,Phylogeography,SNP},
 volume = {2015},
 publisher = {PeerJ Inc.},
 id = {75f314f5-a389-3f31-bafe-751e6eb9bc4b},
 created = {2025-10-30T12:26:00.922Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:09.356Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The post-genomic era is characterized by the direct acquisition and analysis of genomic data with many applications, including the enhancement of the understanding of microbial epidemiology and pathology. However, there are a number of molecular approaches to survey pathogen diversity, and the impact of these different approaches on parameter estimation and inference are not entirely clear. We sequenced whole genomes of bacterial pathogens, Burkholderia pseudomallei, Yersinia pestis, and Brucella spp. (60 new genomes), and combined them with 55 genomes from Gen- Bank to address how different molecular survey approaches (whole genomes, SNPs, and MLST) impact downstream inferences on molecular evolutionary parameters, evolutionary relationships, and trait character associations. We selected isolates for sequencing to represent temporal, geographic origin, and host range variability. We found that substitution rate estimates vary widely among approaches, and that SNP and genomic datasets yielded different but strongly supported phylogenies. MLST yielded poorly supported phylogenies, especially in our low diversity dataset, i.e., Y. pestis. Trait associations showed that B. pseudomallei and Y. pestis phylogenies are significantly associated with geography, irrespective of the molecular survey approach used, while Brucella spp. phylogeny appears to be strongly associated with geography and host origin. We contrast inferences made among monomorphic (clonal) and non-monomorphic bacteria, and between intra- and inter-specific datasets. We also discuss our results in light of underlying assumptions of different approaches.},
 bibtype = {article},
 author = {Castro-Nallar, Eduardo and Hasan, Nur A. and Cebula, Thomas A. and Colwell, Rita R. and Robison, Richard A. and Johnson, W. Evan and Crandall, Keith A.},
 doi = {10.7717/PEERJ.761},
 journal = {PeerJ},
 number = {2}
}

The post-genomic era is characterized by the direct acquisition and analysis of genomic data with many applications, including the enhancement of the understanding of microbial epidemiology and pathology. However, there are a number of molecular approaches to survey pathogen diversity, and the impact of these different approaches on parameter estimation and inference are not entirely clear. We sequenced whole genomes of bacterial pathogens, Burkholderia pseudomallei, Yersinia pestis, and Brucella spp. (60 new genomes), and combined them with 55 genomes from Gen- Bank to address how different molecular survey approaches (whole genomes, SNPs, and MLST) impact downstream inferences on molecular evolutionary parameters, evolutionary relationships, and trait character associations. We selected isolates for sequencing to represent temporal, geographic origin, and host range variability. We found that substitution rate estimates vary widely among approaches, and that SNP and genomic datasets yielded different but strongly supported phylogenies. MLST yielded poorly supported phylogenies, especially in our low diversity dataset, i.e., Y. pestis. Trait associations showed that B. pseudomallei and Y. pestis phylogenies are significantly associated with geography, irrespective of the molecular survey approach used, while Brucella spp. phylogeny appears to be strongly associated with geography and host origin. We contrast inferences made among monomorphic (clonal) and non-monomorphic bacteria, and between intra- and inter-specific datasets. We also discuss our results in light of underlying assumptions of different approaches.

@article{
 title = {Deep-sea hydrothermal vent bacteria related to human pathogenic Vibrio species},
 type = {article},
 year = {2015},
 keywords = {EX25,Genomics,Hydrothermal vent,Vibrio},
 pages = {E2813-E2819},
 volume = {112},
 month = {5},
 publisher = {National Academy of Sciences},
 day = {26},
 id = {e3c54168-8e43-31e7-899e-5492417c8109},
 created = {2025-10-30T12:26:01.085Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:01.085Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Vibrio species are both ubiquitous and abundant in marine coastal waters, estuaries, ocean sediment, and aquaculture settings world-wide. We report here the isolation, characterization, and genome sequence of a novel Vibrio species, Vibrio antiquarius, isolated from a mesophilic bacterial community associated with hydrothermal vents located along the East Pacific Rise, near the southwest coast of Mexico. Genomic and phenotypic analysis revealed V. antiquarius is closely related to pathogenic Vibrio species, namely Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio harveyi, and Vibrio vulnificus, but sufficiently divergent to warrant a separate species status. The V. antiquarius genome encodes genes and operons with ecological functions relevant to the environment conditions of the deep sea and also harbors factors known to be involved in human disease caused by freshwater, coastal, and brackish water vibrios. The presence of virulence factors in this deep-sea Vibrio species suggests a far more fundamental role of these factors for their bacterial host. Comparative genomics revealed a variety of genomic events that may have provided an important driving force in V. antiquarius evolution, facilitating response to environmental conditions of the deep sea.},
 bibtype = {article},
 author = {Hasan, Nur A. and Grim, Christopher J. and Lipp, Erin K. and Rivera, Irma N.G. and Chun, Jongsik and Haley, Bradd J. and Taviani, Elisa and Choi, Seon Young and Hoq, Mozammel and Munk, A. Christine and Brettin, Thomas S. and Bruce, David and Challacombe, Jean F. and Detter, J. Chris and Han, Cliff S. and Eisen, Jonathan A. and Huq, Anwar and Colwell, Rita R.},
 doi = {10.1073/PNAS.1503928112},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 number = {21}
}

Vibrio species are both ubiquitous and abundant in marine coastal waters, estuaries, ocean sediment, and aquaculture settings world-wide. We report here the isolation, characterization, and genome sequence of a novel Vibrio species, Vibrio antiquarius, isolated from a mesophilic bacterial community associated with hydrothermal vents located along the East Pacific Rise, near the southwest coast of Mexico. Genomic and phenotypic analysis revealed V. antiquarius is closely related to pathogenic Vibrio species, namely Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio harveyi, and Vibrio vulnificus, but sufficiently divergent to warrant a separate species status. The V. antiquarius genome encodes genes and operons with ecological functions relevant to the environment conditions of the deep sea and also harbors factors known to be involved in human disease caused by freshwater, coastal, and brackish water vibrios. The presence of virulence factors in this deep-sea Vibrio species suggests a far more fundamental role of these factors for their bacterial host. Comparative genomics revealed a variety of genomic events that may have provided an important driving force in V. antiquarius evolution, facilitating response to environmental conditions of the deep sea.

@article{
 title = {Nontoxigenic Vibrio cholerae Non-O1/O139 isolate from a case of human gastroenteritis in the U.S. Gulf Coast},
 type = {article},
 year = {2015},
 pages = {9-14},
 volume = {53},
 month = {1},
 publisher = {American Society for Microbiology},
 day = {1},
 id = {253d56f2-7939-363e-847f-05a294c6fdf9},
 created = {2025-10-30T12:26:01.101Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:10.565Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {An occurrence of Vibrio cholerae non-O1/O139 gastroenteritis in the U.S. Gulf Coast is reported here. Genomic analysis revealed that the isolate lacked known virulence factors associated with the clinical outcome of a V. cholerae infection but did contain putative genomic islands and other accessory virulence factors. Many of these factors are widespread among environmental strains of V. cholerae, suggesting that there might be additional virulence factors in non-O1/O139 V. cholerae yet to be determined. Phylogenetic analysis revealed that the isolate belonged to a phyletic lineage of environmental V. cholerae isolates associated with sporadic cases of gastroenteritis in the Western Hemisphere, suggesting a need to monitor non-O1/O139 V. cholerae in the interest of public health.},
 bibtype = {article},
 author = {Hasan, Nur A. and Rezayat, Talayeh and Blatz, Peter J. and Choi, Seon Young and Griffitt, Kimberly J. and Rashed, Shah M. and Huq, Anwar and Conger, Nicholas G. and Colwell, Rita R. and Jay Grimes, D.},
 doi = {10.1128/JCM.02187-14},
 journal = {Journal of Clinical Microbiology},
 number = {1}
}

An occurrence of Vibrio cholerae non-O1/O139 gastroenteritis in the U.S. Gulf Coast is reported here. Genomic analysis revealed that the isolate lacked known virulence factors associated with the clinical outcome of a V. cholerae infection but did contain putative genomic islands and other accessory virulence factors. Many of these factors are widespread among environmental strains of V. cholerae, suggesting that there might be additional virulence factors in non-O1/O139 V. cholerae yet to be determined. Phylogenetic analysis revealed that the isolate belonged to a phyletic lineage of environmental V. cholerae isolates associated with sporadic cases of gastroenteritis in the Western Hemisphere, suggesting a need to monitor non-O1/O139 V. cholerae in the interest of public health.

@article{
 title = {An integrated catalog of reference genes in the human gut microbiome},
 type = {article},
 year = {2014},
 pages = {834-841},
 volume = {32},
 id = {a0e09caa-21ea-3246-898e-e25bb46dab51},
 created = {2025-07-07T13:25:05.931Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:53.746Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Many analyses of the human gut microbiome depend on a catalog of reference genes. Existing catalogs for the human gut microbiome are based on samples from single cohorts or on reference genomes or protein sequences, which limits coverage of global microbiome diversity. Here we combined 249 newly sequenced samples of the Metagenomics of the Human Intestinal Tract (MetaHit) project with 1,018 previously sequenced samples to create a cohort from three continents that is at least threefold larger than cohorts used for previous gene catalogs. From this we established the integrated gene catalog (IGC) comprising 9,879,896 genes. The catalog includes close-to-complete sets of genes for most gut microbes, which are also of considerably higher quality than in previous catalogs. Analyses of a group of samples from Chinese and Danish individuals using the catalog revealed country-specific gut microbial signatures. This expanded catalog should facilitate quantitative characterization of metagenomic, metatranscriptomic and metaproteomic data from the gut microbiome to understand its variation across populations in human health and disease. © 2014 Nature America, Inc.},
 bibtype = {article},
 author = {Li, Junhua and Wang, Jun and Jia, Huijue and Cai, Xianghang and Zhong, Huanzi and Feng, Qiang and Sunagawa, Shinichi and Arumugam, Manimozhiyan and Kultima, Jens Roat and Prifti, Edi and Nielsen, Trine and Juncker, Agnieszka Sierakowska and Manichanh, Chaysavanh and Chen, Bing and Zhang, Wenwei and Levenez, Florence and Wang, Juan and Xu, Xun and Xiao, Liang and Liang, Suisha and Zhang, Dongya and Zhang, Zhaoxi and Chen, Weineng and Zhao, Hailong and Al-Aama, Jumana Yousuf and Edris, Sherif and Yang, Huanming and Wang, Jian and Hansen, Torben and Nielsen, Henrik Bjørn and Brunak, Søren and Kristiansen, Karsten and Guarner, Francisco and Pedersen, Oluf and Doré, Joel and Ehrlich, S. Dusko and Bork, Peer},
 doi = {10.1038/nbt.2942},
 journal = {Nature Biotechnology},
 number = {8}
}

Many analyses of the human gut microbiome depend on a catalog of reference genes. Existing catalogs for the human gut microbiome are based on samples from single cohorts or on reference genomes or protein sequences, which limits coverage of global microbiome diversity. Here we combined 249 newly sequenced samples of the Metagenomics of the Human Intestinal Tract (MetaHit) project with 1,018 previously sequenced samples to create a cohort from three continents that is at least threefold larger than cohorts used for previous gene catalogs. From this we established the integrated gene catalog (IGC) comprising 9,879,896 genes. The catalog includes close-to-complete sets of genes for most gut microbes, which are also of considerably higher quality than in previous catalogs. Analyses of a group of samples from Chinese and Danish individuals using the catalog revealed country-specific gut microbial signatures. This expanded catalog should facilitate quantitative characterization of metagenomic, metatranscriptomic and metaproteomic data from the gut microbiome to understand its variation across populations in human health and disease. © 2014 Nature America, Inc.

@article{
 title = {Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes.},
 type = {article},
 year = {2014},
 pages = {822-828},
 volume = {32},
 websites = {http://dx.doi.org/10.1038/nbt.2939\nhttp://www.cbs.dtu.dk/databases/CAG/},
 id = {c35750dd-7d48-3219-bc0e-7dbb34830f04},
 created = {2025-07-07T13:25:06.339Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:54.131Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference databases. De novo segregation of complex metagenomic data into specific biological entities, such as particular bacterial strains or viruses, remains a largely unsolved problem. Here we present a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly of microbial genomes without the need for reference sequences. We demonstrate the method on data from 396 human gut microbiome samples and identify 7,381 co-abundance gene groups (CAGs), including 741 metagenomic species (MGS). We use these to assemble 238 high-quality microbial genomes and identify affiliations between MGS and hundreds of viruses or genetic entities. Our method provides the means for comprehensive profiling of the diversity within complex metagenomic samples.},
 bibtype = {article},
 author = {Nielsen, H Bjørn and Almeida, Mathieu and Juncker, Agnieszka Sierakowska and Rasmussen, Simon and Li, Junhua and Sunagawa, Shinichi and Plichta, Damian R and Gautier, Laurent and Pedersen, Anders G and Le Chatelier, Emmanuelle and Pelletier, Eric and Bonde, Ida and Nielsen, Trine and Manichanh, Chaysavanh and Arumugam, Manimozhiyan and Batto, Jean-Michel and Quintanilha Dos Santos, Marcelo B and Blom, Nikolaj and Borruel, Natalia and Burgdorf, Kristoffer S and Boumezbeur, Fouad and Casellas, Francesc and Doré, Joël and Dworzynski, Piotr and Guarner, Francisco and Hansen, Torben and Hildebrand, Falk and Kaas, Rolf S and Kennedy, Sean and Kristiansen, Karsten and Kultima, Jens Roat and Léonard, Pierre and Levenez, Florence and Lund, Ole and Moumen, Bouziane and Le Paslier, Denis and Pons, Nicolas and Pedersen, Oluf and Prifti, Edi and Qin, Junjie and Raes, Jeroen and Sørensen, Søren and Tap, Julien and Tims, Sebastian and Ussery, David W and Yamada, Takuji and Renault, Pierre and Sicheritz-Ponten, Thomas and Bork, Peer and Wang, Jun and Brunak, Søren and Ehrlich, S Dusko},
 doi = {10.1038/nbt.2939},
 journal = {Nature biotechnology},
 number = {8}
}

Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference databases. De novo segregation of complex metagenomic data into specific biological entities, such as particular bacterial strains or viruses, remains a largely unsolved problem. Here we present a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly of microbial genomes without the need for reference sequences. We demonstrate the method on data from 396 human gut microbiome samples and identify 7,381 co-abundance gene groups (CAGs), including 741 metagenomic species (MGS). We use these to assemble 238 high-quality microbial genomes and identify affiliations between MGS and hundreds of viruses or genetic entities. Our method provides the means for comprehensive profiling of the diversity within complex metagenomic samples.

@article{
 title = {Occurrence in Mexico, 1998-2008, of Vibrio cholerae CTX+ El Tor carrying an additional truncated CTX prophage},
 type = {article},
 year = {2014},
 pages = {9917-9922},
 volume = {111},
 month = {7},
 publisher = {National Academy of Sciences},
 day = {8},
 id = {f1a0e909-ef6d-361f-aa15-19079a39bb6b},
 created = {2025-10-30T12:26:00.905Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:10.388Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The seventh cholera pandemic caused by Vibrio cholerae O1 El Tor (ET) has been superseded in Asia and Africa by altered ET possessing the cholera toxin (CTX) gene of classical (CL) biotype. The CL biotype of V. cholerae was isolated, along with prototypic and altered ET, during the 1991 cholera epidemic in Mexico and subsequently remained endemic until 1997. Microbiological, molecular, and phylogenetic analyses of clinical and environmental V. cholerae isolated in Mexico between 1998 and 2008 revealed important genetic events favoring predominance of ET over CL and altered ET. V. cholerae altered ET was predominant after 1991 but not after 2000. V. cholerae strains isolated between 2001 and 2003 and a majority isolated in 2004 lacked CTX prophage (Φ) genes encoding CTX subunits A and B and repeat sequence transcriptional regulators of ET and CL biotypes: i.e., CTXΦ-. Most CTXΦ- V. cholerae isolated in Mexico between 2001 and 2003 also lacked toxin coregulated pili tcpA whereas some carried either tcpAET or a variant tcpA with noticeable sequence dissimilarity from tcpACL. The tcpA variants were not detected in 2005 after CTXΦ+ ET became dominant. All clinical and environmental V. cholerae O1 strains isolated during 2005-2008 in Mexico were CTXΦ+ ET, carrying an additional truncated CTXΦ instead of RS1 satellite phage. Despite V. cholerae CTXΦ- ET exhibiting heterogeneity in pulsed-field gel electrophoresis patterns, CTXΦ+ ET isolated during 2004-2008 displayed homogeneity and clonal relationship with V. cholerae ET N16961 and V. cholerae ET isolated in Peru.},
 bibtype = {article},
 author = {Alam, Munirul and Rashed, Shah Manzur and Mannan, Shahnewaj Bin and Islam, Tarequl and Lizarraga-Partida, Marcial Leonardo and Delgado, Gabriela and Morales-Espinosa, Rosario and Mendez, Jose Luis and Navarro, Armando and Watanabe, Haruo and Ohnishi, Makoto and Hasan, Nur A. and Huq, Anwar and Sack, R. Bradley and Colwell, Rita R. and Cravioto, Alejandro},
 doi = {10.1073/PNAS.1323408111},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 number = {27}
}

The seventh cholera pandemic caused by Vibrio cholerae O1 El Tor (ET) has been superseded in Asia and Africa by altered ET possessing the cholera toxin (CTX) gene of classical (CL) biotype. The CL biotype of V. cholerae was isolated, along with prototypic and altered ET, during the 1991 cholera epidemic in Mexico and subsequently remained endemic until 1997. Microbiological, molecular, and phylogenetic analyses of clinical and environmental V. cholerae isolated in Mexico between 1998 and 2008 revealed important genetic events favoring predominance of ET over CL and altered ET. V. cholerae altered ET was predominant after 1991 but not after 2000. V. cholerae strains isolated between 2001 and 2003 and a majority isolated in 2004 lacked CTX prophage (Φ) genes encoding CTX subunits A and B and repeat sequence transcriptional regulators of ET and CL biotypes: i.e., CTXΦ-. Most CTXΦ- V. cholerae isolated in Mexico between 2001 and 2003 also lacked toxin coregulated pili tcpA whereas some carried either tcpAET or a variant tcpA with noticeable sequence dissimilarity from tcpACL. The tcpA variants were not detected in 2005 after CTXΦ+ ET became dominant. All clinical and environmental V. cholerae O1 strains isolated during 2005-2008 in Mexico were CTXΦ+ ET, carrying an additional truncated CTXΦ instead of RS1 satellite phage. Despite V. cholerae CTXΦ- ET exhibiting heterogeneity in pulsed-field gel electrophoresis patterns, CTXΦ+ ET isolated during 2004-2008 displayed homogeneity and clonal relationship with V. cholerae ET N16961 and V. cholerae ET isolated in Peru.

@article{
 title = {Genomic and phenotypic characterization of Vibrio cholerae non-O1 isolates from a US gulf coast cholera outbreak},
 type = {article},
 year = {2014},
 volume = {9},
 month = {4},
 publisher = {Public Library of Science},
 day = {1},
 id = {3012e4bf-7f88-3148-b9b0-65836b26f63a},
 created = {2025-10-30T12:26:00.922Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:09.241Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Between November 2010, and May 2011, eleven cases of cholera, unrelated to a concurrent outbreak on the island of Hispaniola, were recorded, and the causative agent, Vibrio cholerae serogroup O75, was traced to oysters harvested from Apalachicola Bay, Florida. From the 11 diagnosed cases, eight isolates of V. cholerae were isolated and their genomes were sequenced. Genomic analysis demonstrated the presence of a suite of mobile elements previously shown to be involved in the disease process of cholera (ctxAB, VPI-1 and -2, and a VSP-II like variant) and a phylogenomic analysis showed the isolates to be sister taxa to toxigenic V. cholerae V51 serogroup O141, a clinical strain isolated 23 years earlier. Toxigenic V. cholerae O75 has been repeatedly isolated from clinical cases in the southeastern United States and toxigenic V. cholerae O141 isolates have been isolated globally from clinical cases over several decades. Comparative genomics, phenotypic analyses, and a Caenorhabditis elegans model of infection for the isolates were conducted. This analysis coupled with isolation data of V. cholerae O75 and O141 suggests these strains may represent an underappreciated clade of choleracausing strains responsible for significant disease burden globally.},
 bibtype = {article},
 author = {Haley, Bradd J. and Choi, Seon Young and Grim, Christopher J. and Onifade, Tiffiani J. and Cinar, Hediye N. and Tall, Ben D. and Taviani, Elisa and Hasan, Nur A. and Abdullah, Abdulshakur H. and Carter, Laurenda and Sahu, Surasri N. and Kothary, Mahendra H. and Chen, Arlene and Baker, Ron and Hutchinson, Richard and Blackmore, Carina and Cebula, Thomas A. and Huq, Anwar and Colwell, Rita R.},
 doi = {10.1371/JOURNAL.PONE.0086264},
 journal = {PLoS ONE},
 number = {4}
}

Between November 2010, and May 2011, eleven cases of cholera, unrelated to a concurrent outbreak on the island of Hispaniola, were recorded, and the causative agent, Vibrio cholerae serogroup O75, was traced to oysters harvested from Apalachicola Bay, Florida. From the 11 diagnosed cases, eight isolates of V. cholerae were isolated and their genomes were sequenced. Genomic analysis demonstrated the presence of a suite of mobile elements previously shown to be involved in the disease process of cholera (ctxAB, VPI-1 and -2, and a VSP-II like variant) and a phylogenomic analysis showed the isolates to be sister taxa to toxigenic V. cholerae V51 serogroup O141, a clinical strain isolated 23 years earlier. Toxigenic V. cholerae O75 has been repeatedly isolated from clinical cases in the southeastern United States and toxigenic V. cholerae O141 isolates have been isolated globally from clinical cases over several decades. Comparative genomics, phenotypic analyses, and a Caenorhabditis elegans model of infection for the isolates were conducted. This analysis coupled with isolation data of V. cholerae O75 and O141 suggests these strains may represent an underappreciated clade of choleracausing strains responsible for significant disease burden globally.

@article{
 title = {Longitudinal analysis of microbial interaction between humans and the indoor environment},
 type = {article},
 year = {2014},
 pages = {1048-1052},
 volume = {345},
 month = {8},
 publisher = {American Association for the Advancement of Science},
 day = {29},
 id = {5f2e4964-01e0-3af0-9bf9-d2776b7116ef},
 created = {2025-10-30T12:26:00.943Z},
 accessed = {2025-10-30},
 file_attached = {false},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:00.943Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The bacteria that colonize humans and our built environments have the potential to influence our health. Microbial communities associated with seven families and their homes over 6 weeks were assessed, including three families that moved their home. Microbial communities differed substantially among homes, and the home microbiome was largely sourced from humans. The microbiota in each home were identifiable by family. Network analysis identified humans as the primary bacterial vector, and a Bayesian method significantly matched individuals to their dwellings. Draft genomes of potential human pathogens observed on a kitchen counter could be matched to the hands of occupants. After a house move, the microbial community in the new house rapidly converged on the microbial community of the occupants' former house, suggesting rapid colonization by the family's microbiota.},
 bibtype = {article},
 author = {Lax, Simon and Smith, Daniel P. and Hampton-Marcell, Jarrad and Owens, Sarah M. and Handley, Kim M. and Scott, Nicole M. and Gibbons, Sean M. and Larsen, Peter and Shogan, Benjamin D. and Weiss, Sophie and Metcalf, Jessica L. and Ursell, Luke K. and Vázquez-Baeza, Yoshiki and Van Treuren, Will and Hasan, Nur A. and Gibson, Molly K. and Colwell, Rita and Dantas, Gautam and Knight, Rob and Gilbert, Jack A.},
 doi = {10.1126/SCIENCE.1254529},
 journal = {Science},
 number = {6200}
}

The bacteria that colonize humans and our built environments have the potential to influence our health. Microbial communities associated with seven families and their homes over 6 weeks were assessed, including three families that moved their home. Microbial communities differed substantially among homes, and the home microbiome was largely sourced from humans. The microbiota in each home were identifiable by family. Network analysis identified humans as the primary bacterial vector, and a Bayesian method significantly matched individuals to their dwellings. Draft genomes of potential human pathogens observed on a kitchen counter could be matched to the hands of occupants. After a house move, the microbial community in the new house rapidly converged on the microbial community of the occupants' former house, suggesting rapid colonization by the family's microbiota.

@article{
 title = {Molecular diversity and predictability of Vibrio parahaemolyticus along the Georgian coastal zone of the Black Sea},
 type = {article},
 year = {2014},
 keywords = {Aquatic microbiology,Black Sea,Predictive modeling,Vibrio parahaemolyticus,Vibrionaceae},
 volume = {5},
 publisher = {Frontiers Research Foundation},
 id = {94278af4-a3f3-36d1-be30-f55e17a01e97},
 created = {2025-10-30T12:26:01.058Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:09.891Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Vibrio parahaemolyticus is a leading cause of seafood-related gastroenteritis and is also an autochthonous member of marine and estuarine environments worldwide. One-hundred seventy strains of V. parahaemolyticus were isolated from water and plankton samples collected along the Georgian coast of the Black Sea during 28 months of sample collection. All isolated strains were tested for presence of tlh, trh, and tdh. A subset of strains were serotyped and tested for additional factors and markers of pandemicity. Twenty-six serotypes, five of which are clinically relevant, were identified. Although all 170 isolates were negative for tdh, trh, and the Kanagawa Phenomenon, 7 possessed the GS-PCR sequence and 27 the 850 bp sequence of V. parahaemolyticus pandemic strains. The V. parahaemolyticus population in the Black Sea was estimated to be genomically heterogeneous by rep-PCR and the serodiversity observed did not correlate with rep-PCR genomic diversity. Statistical modeling was used to predict presence of V. parahaemolyticus as a function of water temperature, with strongest concordance observed for Green Cape site samples (Percent of total variance = 70, P < 0.001). Results demonstrate a diverse population of V. parahaemolyticus in the Black Sea, some of which carry pandemic markers, with increased water temperature correlated to an increase in abundance of V. parahaemolyticus. © 2014 Haley, Kokashvili, Tskshvediani, Janelidze, Mitaishvili, Grim, Constantin de Magny, Chen, Taviani, Eliashvili, Tediashvili, Whitehouse, Colwell and Huq.},
 bibtype = {article},
 author = {Haley, Bradd J. and Kokashvili, Tamar and Tskshvediani, Ana and Janelidze, Nino and Mitaishvili, Nino and Grim, Christopher J. and de Magny, Guillaume Constantin and Chen, Arlene J. and Taviani, Elisa and Eliashvili, Tamar and Tediashvili, Marina and Whitehouse, Chris A. and Colwell, Rita R. and Huq, Anwar},
 doi = {10.3389/FMICB.2014.00045},
 journal = {Frontiers in Microbiology},
 number = {FEB}
}

Vibrio parahaemolyticus is a leading cause of seafood-related gastroenteritis and is also an autochthonous member of marine and estuarine environments worldwide. One-hundred seventy strains of V. parahaemolyticus were isolated from water and plankton samples collected along the Georgian coast of the Black Sea during 28 months of sample collection. All isolated strains were tested for presence of tlh, trh, and tdh. A subset of strains were serotyped and tested for additional factors and markers of pandemicity. Twenty-six serotypes, five of which are clinically relevant, were identified. Although all 170 isolates were negative for tdh, trh, and the Kanagawa Phenomenon, 7 possessed the GS-PCR sequence and 27 the 850 bp sequence of V. parahaemolyticus pandemic strains. The V. parahaemolyticus population in the Black Sea was estimated to be genomically heterogeneous by rep-PCR and the serodiversity observed did not correlate with rep-PCR genomic diversity. Statistical modeling was used to predict presence of V. parahaemolyticus as a function of water temperature, with strongest concordance observed for Green Cape site samples (Percent of total variance = 70, P < 0.001). Results demonstrate a diverse population of V. parahaemolyticus in the Black Sea, some of which carry pandemic markers, with increased water temperature correlated to an increase in abundance of V. parahaemolyticus. © 2014 Haley, Kokashvili, Tskshvediani, Janelidze, Mitaishvili, Grim, Constantin de Magny, Chen, Taviani, Eliashvili, Tediashvili, Whitehouse, Colwell and Huq.

@article{
 title = {Validation of high throughput sequencing and microbial forensics applications},
 type = {article},
 year = {2014},
 keywords = {Bioinformatics,High throughput sequencing,Library preparation,Microbial forensics,Sample preparation,Validation},
 volume = {5},
 month = {7},
 publisher = {BioMed Central Ltd},
 day = {30},
 id = {8ea41f85-3f24-3d1a-830e-5802cfba1856},
 created = {2025-10-30T12:26:01.143Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:09.604Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {High throughput sequencing (HTS) generates large amounts of high quality sequence data for microbial genomics. The value of HTS for microbial forensics is the speed at which evidence can be collected and the power to characterize microbial-related evidence to solve biocrimes and bioterrorist events. As HTS technologies continue to improve, they provide increasingly powerful sets of tools to support the entire field of microbial forensics. Accurate, credible results allow analysis and interpretation, significantly influencing the course and/or focus of an investigation, and can impact the response of the government to an attack having individual, political, economic or military consequences. Interpretation of the results of microbial forensic analyses relies on understanding the performance and limitations of HTS methods, including analytical processes, assays and data interpretation. The utility of HTS must be defined carefully within established operating conditions and tolerances. Validation is essential in the development and implementation of microbial forensics methods used for formulating investigative leads attribution. HTS strategies vary, requiring guiding principles for HTS system validation. Three initial aspects of HTS, irrespective of chemistry, instrumentation or software are: 1) sample preparation, 2) sequencing, and 3) data analysis. Criteria that should be considered for HTS validation for microbial forensics are presented here. Validation should be defined in terms of specific application and the criteria described here comprise a foundation for investigators to establish, validate and implement HTS as a tool in microbial forensics, enhancing public safety and national security. © 2014 Budowle et al.; licensee BioMed Central Ltd.},
 bibtype = {article},
 author = {Budowle, Bruce and Connell, Nancy D. and Bielecka-Oder, Anna and Colwell, Rita R. and Corbett, Cindi R. and Fletcher, Jacqueline and Forsman, Mats and Kadavy, Dana R. and Markotic, Alemka and Morse, Stephen A. and Murch, Randall S. and Sajantila, Antti and Schmedes, Sarah E. and Ternus, Krista L. and Turner, Stephen D. and Minot, Samuel},
 doi = {10.1186/2041-2223-5-9},
 journal = {Investigative Genetics},
 number = {1}
}

High throughput sequencing (HTS) generates large amounts of high quality sequence data for microbial genomics. The value of HTS for microbial forensics is the speed at which evidence can be collected and the power to characterize microbial-related evidence to solve biocrimes and bioterrorist events. As HTS technologies continue to improve, they provide increasingly powerful sets of tools to support the entire field of microbial forensics. Accurate, credible results allow analysis and interpretation, significantly influencing the course and/or focus of an investigation, and can impact the response of the government to an attack having individual, political, economic or military consequences. Interpretation of the results of microbial forensic analyses relies on understanding the performance and limitations of HTS methods, including analytical processes, assays and data interpretation. The utility of HTS must be defined carefully within established operating conditions and tolerances. Validation is essential in the development and implementation of microbial forensics methods used for formulating investigative leads attribution. HTS strategies vary, requiring guiding principles for HTS system validation. Three initial aspects of HTS, irrespective of chemistry, instrumentation or software are: 1) sample preparation, 2) sequencing, and 3) data analysis. Criteria that should be considered for HTS validation for microbial forensics are presented here. Validation should be defined in terms of specific application and the criteria described here comprise a foundation for investigators to establish, validate and implement HTS as a tool in microbial forensics, enhancing public safety and national security. © 2014 Budowle et al.; licensee BioMed Central Ltd.

@article{
 title = {Microbial community profiling of human saliva using shotgun metagenomic sequencing},
 type = {article},
 year = {2014},
 volume = {9},
 month = {5},
 publisher = {Public Library of Science},
 day = {20},
 id = {52d2aef7-0c65-334f-9953-0c91b37bfc75},
 created = {2025-10-30T12:26:01.474Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:10.042Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Human saliva is clinically informative of both oral and general health. Since next generation shotgun sequencing (NGS) is now widely used to identify and quantify bacteria, we investigated the bacterial flora of saliva microbiomes of two healthy volunteers and five datasets from the Human Microbiome Project, along with a control dataset containing short NGS reads from bacterial species representative of the bacterial flora of human saliva. GENIUS, a system designed to identify and quantify bacterial species using unassembled short NGS reads was used to identify the bacterial species comprising the microbiomes of the saliva samples and datasets. Results, achieved within minutes and at greater than 90% accuracy, showed more than 175 bacterial species comprised the bacterial flora of human saliva, including bacteria known to be commensal human flora but also Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, and Gamma proteobacteria. Basic Local Alignment Search Tool (BLASTn) analysis in parallel, reported ca. five times more species than those actually comprising the in silico sample. Both GENIUSand BLAST analyses of saliva samples identified major genera comprising the bacterial flora of saliva, but GENIUS provided a more precise description of species composition, identifying to strain in most cases and delivered results at least 10,000 times faster. Therefore, GENIUS offers a facile and accurate system for identification and quantification of bacterial species and/or strains in metagenomic samples. © 2014 Hasan et al.},
 bibtype = {article},
 author = {Hasan, Nur A. and Young, Brian A. and Minard-Smith, Angela T. and Saeed, Kelly and Li, Huai and Heizer, Esley M. and McMillan, Nancy J. and Isom, Richard and Abdullah, Abdul Shakur and Bornman, Daniel M. and Faith, Seth A. and Choi, Seon Young and Dickens, Michael L. and Cebula, Thomas A. and Colwell, Rita R.},
 doi = {10.1371/JOURNAL.PONE.0097699},
 journal = {PLoS ONE},
 number = {5}
}

Human saliva is clinically informative of both oral and general health. Since next generation shotgun sequencing (NGS) is now widely used to identify and quantify bacteria, we investigated the bacterial flora of saliva microbiomes of two healthy volunteers and five datasets from the Human Microbiome Project, along with a control dataset containing short NGS reads from bacterial species representative of the bacterial flora of human saliva. GENIUS, a system designed to identify and quantify bacterial species using unassembled short NGS reads was used to identify the bacterial species comprising the microbiomes of the saliva samples and datasets. Results, achieved within minutes and at greater than 90% accuracy, showed more than 175 bacterial species comprised the bacterial flora of human saliva, including bacteria known to be commensal human flora but also Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, and Gamma proteobacteria. Basic Local Alignment Search Tool (BLASTn) analysis in parallel, reported ca. five times more species than those actually comprising the in silico sample. Both GENIUSand BLAST analyses of saliva samples identified major genera comprising the bacterial flora of saliva, but GENIUS provided a more precise description of species composition, identifying to strain in most cases and delivered results at least 10,000 times faster. Therefore, GENIUS offers a facile and accurate system for identification and quantification of bacterial species and/or strains in metagenomic samples. © 2014 Hasan et al.

@article{
 title = {Metagenomic species profiling using universal phylogenetic marker genes},
 type = {article},
 year = {2013},
 pages = {1196-1199},
 volume = {10},
 id = {52098d3a-bc60-3955-9662-ed6dfc4b200c},
 created = {2025-07-07T13:25:04.758Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:52.790Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {To quantify known and unknown microorganisms at species-level resolution using shotgun sequencing data, we developed a method that establishes metagenomic operational taxonomic units (mOTUs) based on single-copy phylogenetic marker genes. Applied to 252 human fecal samples, the method revealed that on average 43% of the species abundance and 58% of the richness cannot be captured by current reference genome-based methods. An implementation of the method is available at http://www.bork.embl.de/software/mOTU/. © 2013 Nature America, Inc.},
 bibtype = {article},
 author = {Sunagawa, Shinichi and Mende, Daniel R. and Zeller, Georg and Izquierdo-Carrasco, Fernando and Berger, Simon A. and Kultima, Jens Roat and Coelho, Luis Pedro and Arumugam, Manimozhiyan and Tap, Julien and Nielsen, Henrik Bjørn and Rasmussen, Simon and Brunak, Søren and Pedersen, Oluf and Guarner, Francisco and De Vos, Willem M. and Wang, Jun and Li, Junhua and Doré, Joël and Dusko Ehrlich, S. and Stamatakis, Alexandros and Bork, Peer},
 doi = {10.1038/nmeth.2693},
 journal = {Nature Methods},
 number = {12}
}

To quantify known and unknown microorganisms at species-level resolution using shotgun sequencing data, we developed a method that establishes metagenomic operational taxonomic units (mOTUs) based on single-copy phylogenetic marker genes. Applied to 252 human fecal samples, the method revealed that on average 43% of the species abundance and 58% of the richness cannot be captured by current reference genome-based methods. An implementation of the method is available at http://www.bork.embl.de/software/mOTU/. © 2013 Nature America, Inc.

@article{
 title = {Richness of human gut microbiome correlates with metabolic markers.},
 type = {article},
 year = {2013},
 keywords = {Adiposity,Adult,Bacteria,Bacteria: classification,Bacteria: genetics,Bacteria: isolation & purification,Biological Markers,Biological Markers: metabolism,Body Mass Index,Case-Control Studies,Diet,Dyslipidemias,Dyslipidemias: microbiology,Energy Metabolism,Europe,Europe: ethnology,European Continental Ancestry Group,Female,Gastrointestinal Tract,Gastrointestinal Tract: microbiology,Genes, Bacterial,Humans,Inflammation,Inflammation: microbiology,Insulin Resistance,Male,Metagenome,Metagenome: genetics,Obesity,Obesity: metabolism,Obesity: microbiology,Overweight,Overweight: metabolism,Overweight: microbiology,Phylogeny,Thinness,Thinness: microbiology,Weight Gain,Weight Loss},
 pages = {541-6},
 volume = {500},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/23985870},
 month = {8},
 day = {29},
 id = {ff53eeab-0e60-3cc3-816e-c2b4ff3fcbe0},
 created = {2025-07-07T13:25:05.209Z},
 accessed = {2013-10-17},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:53.092Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.},
 bibtype = {article},
 author = {Le Chatelier, Emmanuelle and Nielsen, Trine and Qin, Junjie and Prifti, Edi and Hildebrand, Falk and Falony, Gwen and Almeida, Mathieu and Arumugam, Manimozhiyan and Batto, Jean-Michel and Kennedy, Sean and Leonard, Pierre and Li, Junhua and Burgdorf, Kristoffer and Grarup, Niels and Jørgensen, Torben and Brandslund, Ivan and Nielsen, Henrik Bjørn and Juncker, Agnieszka S and Bertalan, Marcelo and Levenez, Florence and Pons, Nicolas and Rasmussen, Simon and Sunagawa, Shinichi and Tap, Julien and Tims, Sebastian and Zoetendal, Erwin G and Brunak, Søren and Clément, Karine and Doré, Joël and Kleerebezem, Michiel and Kristiansen, Karsten and Renault, Pierre and Sicheritz-Ponten, Thomas and de Vos, Willem M and Zucker, Jean-Daniel and Raes, Jeroen and Hansen, Torben and Bork, Peer and Wang, Jun and Ehrlich, S Dusko and Pedersen, Oluf and Guedon, Eric and Delorme, Christine and Layec, Séverine and Khaci, Ghalia and van de Guchte, Maarten and Vandemeulebrouck, Gaetana and Jamet, Alexandre and Dervyn, Rozenn and Sanchez, Nicolas and Maguin, Emmanuelle and Haimet, Florence and Winogradski, Yohanan and Cultrone, Antonella and Leclerc, Marion and Juste, Catherine and Blottière, Hervé and Pelletier, Eric and LePaslier, Denis and Artiguenave, François and Bruls, Thomas and Weissenbach, Jean and Turner, Keith and Parkhill, Julian and Antolin, Maria and Manichanh, Chaysavanh and Casellas, Francesc and Boruel, Natalia and Varela, Encarna and Torrejon, Antonio and Guarner, Francisco and Denariaz, Gérard and Derrien, Muriel and van Hylckama Vlieg, Johan E T and Veiga, Patrick and Oozeer, Raish and Knol, Jan and Rescigno, Maria and Brechot, Christian and M'Rini, Christine and Mérieux, Alexandre and Yamada, Takuji},
 doi = {10.1038/nature12506},
 journal = {Nature},
 number = {7464}
}

We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.

@article{
 title = {The chemical interactome space between the human host and the genetically defined gut metabotypes},
 type = {article},
 year = {2013},
 keywords = {microbiome; metabolic network; drugs; protein inte},
 pages = {730-742},
 volume = {7},
 id = {40ec2558-926a-3d25-bf3d-b2ef1c166313},
 created = {2025-07-07T13:25:05.569Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:53.425Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {The bacteria that colonize the gastrointestinal tracts of mammals represent a highly selected microbiome that has a profound influence on human physiology by shaping the host's metabolic and immune system activity. Despite the recent advances on the biological principles that underlie microbial symbiosis in the gut of mammals, mechanistic understanding of the contributions of the gut microbiome and how variations in the metabotypes are linked to the host health are obscure. Here, we mapped the entire metabolic potential of the gut microbiome based solely on metagenomics sequencing data derived from fecal samples of 124 Europeans (healthy, obese and with inflammatory bowel disease). Interestingly, three distinct clusters of individuals with high, medium and low metabolic potential were observed. By illustrating these results in the context of bacterial population, we concluded that the abundance of the Prevotella genera is a key factor indicating a low metabolic potential. These metagenome-based metabolic signatures were used to study the interaction networks between bacteria-specific metabolites and human proteins. We found that thirty-three such metabolites interact with disease-relevant protein complexes several of which are highly expressed in cells and tissues involved in the signaling and shaping of the adaptive immune system and associated with squamous cell carcinoma and bladder cancer. From this set of metabolites, eighteen are present in DrugBank providing evidence that we carry a natural pharmacy in our guts. Furthermore, we established connections between the systemic effects of non-antibiotic drugs and the gut microbiome of relevance to drug side effects and health-care solutions. © 2013 International Society for Microbial Ecology All rights reserved.},
 bibtype = {article},
 author = {Jacobsen, Ulrik Plesner and Nielsen, Henrik Bjorn and Hildebrand, Falk and Raes, Jeroen and Sicheritz-Ponten, Thomas and Kouskoumvekaki, Irene and Panagiotou, Gianni},
 doi = {10.1038/ismej.2012.141},
 journal = {ISME Journal},
 number = {4}
}

The bacteria that colonize the gastrointestinal tracts of mammals represent a highly selected microbiome that has a profound influence on human physiology by shaping the host's metabolic and immune system activity. Despite the recent advances on the biological principles that underlie microbial symbiosis in the gut of mammals, mechanistic understanding of the contributions of the gut microbiome and how variations in the metabotypes are linked to the host health are obscure. Here, we mapped the entire metabolic potential of the gut microbiome based solely on metagenomics sequencing data derived from fecal samples of 124 Europeans (healthy, obese and with inflammatory bowel disease). Interestingly, three distinct clusters of individuals with high, medium and low metabolic potential were observed. By illustrating these results in the context of bacterial population, we concluded that the abundance of the Prevotella genera is a key factor indicating a low metabolic potential. These metagenome-based metabolic signatures were used to study the interaction networks between bacteria-specific metabolites and human proteins. We found that thirty-three such metabolites interact with disease-relevant protein complexes several of which are highly expressed in cells and tissues involved in the signaling and shaping of the adaptive immune system and associated with squamous cell carcinoma and bladder cancer. From this set of metabolites, eighteen are present in DrugBank providing evidence that we carry a natural pharmacy in our guts. Furthermore, we established connections between the systemic effects of non-antibiotic drugs and the gut microbiome of relevance to drug side effects and health-care solutions. © 2013 International Society for Microbial Ecology All rights reserved.

@article{
 title = {A new integrative conjugative element detected in haitian isolates of vibrio cholerae non-O1/non-O139},
 type = {article},
 year = {2013},
 keywords = {Haiti,Integrative conjugative elements,Non-O1/non-O139,Vibrio cholerae},
 pages = {891-893},
 volume = {164},
 month = {11},
 id = {77ef386a-5206-3f41-bdbe-9b51051dd46b},
 created = {2025-10-30T12:26:00.910Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:03.037Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The presence of SXT/R391-related integrating conjugative elements (ICEs) in Vibrio cholerae O1 and non-O1/non-O139 isolated from clinical and environmental samples in Haiti in 2010 was studied. The main finding of this work was the identification of the novel ICE. VchHai2 among closely related V. cholerae non-O1/non-O139 clinical strains. The mosaic structure of this element confirms the role of ICEs as efficient recombination systems whereby new genetic material can be acquired and exchanged, according V. cholerae strains new accessory functions. © 2013 Institut Pasteur.},
 bibtype = {article},
 author = {Ceccarelli, Daniela and Spagnoletti, Matteo and Hasan, Nur A. and Lansing, Stephanie and Huq, Anwar and Colwell, Rita R.},
 doi = {10.1016/J.RESMIC.2013.08.004},
 journal = {Research in Microbiology},
 number = {9}
}

The presence of SXT/R391-related integrating conjugative elements (ICEs) in Vibrio cholerae O1 and non-O1/non-O139 isolated from clinical and environmental samples in Haiti in 2010 was studied. The main finding of this work was the identification of the novel ICE. VchHai2 among closely related V. cholerae non-O1/non-O139 clinical strains. The mosaic structure of this element confirms the role of ICEs as efficient recombination systems whereby new genetic material can be acquired and exchanged, according V. cholerae strains new accessory functions. © 2013 Institut Pasteur.

@article{
 title = {Distribution and dynamics of epidemic and pandemic Vibrio parahaemolyticus virulence factors},
 type = {article},
 year = {2013},
 keywords = {Epidemic strains,O3:K6,PAI,Pandemic strains,Tdh,Trh,V. parahaemolyticus,Virulence markers},
 volume = {3},
 id = {e914acbe-81fc-3902-b10c-3ad64fb7bc71},
 created = {2025-10-30T12:26:01.141Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:10.271Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Vibrio parahaemolyticus, autochthonous to estuarine, marine, and coastal environments throughout the world, is the causative agent of food-borne gastroenteritis. More than 80 serotypes have been described worldwide, based on antigenic properties of the somatic (O) and capsular (K) antigens. Serovar O3:K6 emerged in India in 1996 and subsequently was isolated worldwide, leading to the conclusion that the first V. parahaemolyticus pandemic had taken place. Most strains of V. parahaemolyticus isolated from the environment or seafood, in contrast to clinical strains, do not produce a thermostable direct hemolysin (TDH) and/or a TDH-related hemolysin (TRH). Type 3 secretion systems (T3SSs), needle-like apparatuses able to deliver bacterial effectors into host cytoplasm, were identified as triggering cytotoxicity and enterotoxicity. Type 6 secretion systems (T6SS) predicted to be involved in intracellular trafficking and vesicular transport appear to play a role in V. parahaemolyticus virulence. Recent advances in V. parahaemolyticus genomics identified several pathogenicity islands (VpaIs) located on either chromosome in both epidemic and pandemic strains and comprising additional colonization factors, such as restriction-modification complexes, chemotaxis proteins, classical bacterial surface virulence factors, and putative colicins. Furthermore, studies indicate strains lacking toxins and genomic regions associated with pathogenicity may also be pathogenic, suggesting other important virulence factors remain to be identified. The unique repertoire of virulence factors identified to date, their occurrence and distribution in both epidemic and pandemic strains worldwide are described, with the aim of highlighting the complexity of V. parahaemolyticus pathogenicity as well as its dynamic genome. © 2013 Ceccarelli, Hasan, Huq and Colwell.},
 bibtype = {article},
 author = {Ceccarelli, Daniela and Hasan, Nur A. and Huq, Anwar and Colwell, Rita R.},
 doi = {10.3389/FCIMB.2013.00097},
 journal = {Frontiers in Cellular and Infection Microbiology},
 number = {DEC}
}

Vibrio parahaemolyticus, autochthonous to estuarine, marine, and coastal environments throughout the world, is the causative agent of food-borne gastroenteritis. More than 80 serotypes have been described worldwide, based on antigenic properties of the somatic (O) and capsular (K) antigens. Serovar O3:K6 emerged in India in 1996 and subsequently was isolated worldwide, leading to the conclusion that the first V. parahaemolyticus pandemic had taken place. Most strains of V. parahaemolyticus isolated from the environment or seafood, in contrast to clinical strains, do not produce a thermostable direct hemolysin (TDH) and/or a TDH-related hemolysin (TRH). Type 3 secretion systems (T3SSs), needle-like apparatuses able to deliver bacterial effectors into host cytoplasm, were identified as triggering cytotoxicity and enterotoxicity. Type 6 secretion systems (T6SS) predicted to be involved in intracellular trafficking and vesicular transport appear to play a role in V. parahaemolyticus virulence. Recent advances in V. parahaemolyticus genomics identified several pathogenicity islands (VpaIs) located on either chromosome in both epidemic and pandemic strains and comprising additional colonization factors, such as restriction-modification complexes, chemotaxis proteins, classical bacterial surface virulence factors, and putative colicins. Furthermore, studies indicate strains lacking toxins and genomic regions associated with pathogenicity may also be pathogenic, suggesting other important virulence factors remain to be identified. The unique repertoire of virulence factors identified to date, their occurrence and distribution in both epidemic and pandemic strains worldwide are described, with the aim of highlighting the complexity of V. parahaemolyticus pathogenicity as well as its dynamic genome. © 2013 Ceccarelli, Hasan, Huq and Colwell.

@article{
 title = {A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus) and humans (Homo sapiens)},
 type = {article},
 year = {2012},
 pages = {514},
 volume = {13},
 websites = {BMC Genomics},
 publisher = {BMC Genomics},
 id = {8a93a304-b49f-3cf2-bb6e-571fa847c61b},
 created = {2025-07-07T13:25:04.407Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:52.457Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {BACKGROUND: Guinea pig (Cavia porcellus) is an important model for human intestinal research. We have characterized the faecal microbiota of 60 guinea pigs using Illumina shotgun metagenomics, and used this data to compile a gene catalogue of its prevalent microbiota. Subsequently, we compared the guinea pig microbiome to existing human gut metagenome data from the MetaHIT project.\n\nRESULTS: We found that the bacterial richness obtained for human samples was lower than for guinea pig samples. The intestinal microbiotas of both species were dominated by the two phyla Bacteroidetes and Firmicutes, but at genus level, the majority of identified genera (320 of 376) were differently abundant in the two hosts. For example, the guinea pig contained considerably more of the mucin-degrading Akkermansia, as well as of the methanogenic archaea Methanobrevibacter than found in humans. Most microbiome functional categories were less abundant in guinea pigs than in humans. Exceptions included functional categories possibly reflecting dehydration/rehydration stress in the guinea pig intestine. Finally, we showed that microbiological databases have serious anthropocentric biases, which impacts model organism research.\n\nCONCLUSIONS: The results lay the foundation for future gastrointestinal research applying guinea pigs as models for humans.},
 bibtype = {article},
 author = {Hildebrand, Falk and Ebersbach, Tine and Nielsen, Henrik and Li, Xiaoping and Sonne, Si and Bertalan, Marcelo and Dimitrov, Peter and Madsen, Lise and Qin, Junjie and Wang, Jun and Raes, Jeroen and Kristiansen, Karsten and Licht, Tine},
 doi = {10.1186/1471-2164-13-514},
 journal = {BMC Genomics},
 number = {1}
}

BACKGROUND: Guinea pig (Cavia porcellus) is an important model for human intestinal research. We have characterized the faecal microbiota of 60 guinea pigs using Illumina shotgun metagenomics, and used this data to compile a gene catalogue of its prevalent microbiota. Subsequently, we compared the guinea pig microbiome to existing human gut metagenome data from the MetaHIT project.\n\nRESULTS: We found that the bacterial richness obtained for human samples was lower than for guinea pig samples. The intestinal microbiotas of both species were dominated by the two phyla Bacteroidetes and Firmicutes, but at genus level, the majority of identified genera (320 of 376) were differently abundant in the two hosts. For example, the guinea pig contained considerably more of the mucin-degrading Akkermansia, as well as of the methanogenic archaea Methanobrevibacter than found in humans. Most microbiome functional categories were less abundant in guinea pigs than in humans. Exceptions included functional categories possibly reflecting dehydration/rehydration stress in the guinea pig intestine. Finally, we showed that microbiological databases have serious anthropocentric biases, which impacts model organism research.\n\nCONCLUSIONS: The results lay the foundation for future gastrointestinal research applying guinea pigs as models for humans.

@article{
 title = {Enterotypes of the human gut microbiome.},
 type = {article},
 year = {2011},
 pages = {174-180},
 volume = {473},
 id = {0041b61a-723c-3991-b174-22a33b01ef15},
 created = {2025-07-07T13:25:04.040Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:52.100Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.},
 bibtype = {article},
 author = {Arumugam, Manimozhiyan and Raes, Jeroen and Pelletier, Eric and Le Paslier, Denis and Yamada, Takuji and Mende, Daniel R and Fernandes, Gabriel R and Tap, Julien and Bruls, Thomas and Batto, Jean-Michel and Bertalan, Marcelo and Borruel, Natalia and Casellas, Francesc and Fernandez, Leyden and Gautier, Laurent and Hansen, Torben and Hattori, Masahira and Hayashi, Tetsuya and Kleerebezem, Michiel and Kurokawa, Ken and Leclerc, Marion and Levenez, Florence and Manichanh, Chaysavanh and Nielsen, H Bjørn and Nielsen, Trine and Pons, Nicolas and Poulain, Julie and Qin, Junjie and Sicheritz-Ponten, Thomas and Tims, Sebastian and Torrents, David and Ugarte, Edgardo and Zoetendal, Erwin G and Wang, Jun and Guarner, Francisco and Pedersen, Oluf and de Vos, Willem M and Brunak, Søren and Doré, Joel and Antolín, María and Artiguenave, François and Blottiere, Hervé M and Almeida, Mathieu and Brechot, Christian and Cara, Carlos and Chervaux, Christian and Cultrone, Antonella and Delorme, Christine and Denariaz, Gérard and Dervyn, Rozenn and Foerstner, Konrad U and Friss, Carsten and van de Guchte, Maarten and Guedon, Eric and Haimet, Florence and Huber, Wolfgang and van Hylckama-Vlieg, Johan and Jamet, Alexandre and Juste, Catherine and Kaci, Ghalia and Knol, Jan and Lakhdari, Omar and Layec, Severine and Le Roux, Karine and Maguin, Emmanuelle and Mérieux, Alexandre and Melo Minardi, Raquel and M'rini, Christine and Muller, Jean and Oozeer, Raish and Parkhill, Julian and Renault, Pierre and Rescigno, Maria and Sanchez, Nicolas and Sunagawa, Shinichi and Torrejon, Antonio and Turner, Keith and Vandemeulebrouck, Gaetana and Varela, Encarna and Winogradsky, Yohanan and Zeller, Georg and Weissenbach, Jean and Ehrlich, S Dusko and Bork, Peer},
 doi = {10.1038/nature10187},
 journal = {Nature},
 number = {7346}
}

Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.

@article{
 title = {A human gut microbial gene catalogue established by metagenomic sequencing},
 type = {article},
 year = {2010},
 pages = {59-65},
 volume = {464},
 id = {0ec10282-10aa-3437-a5a9-ce5815749e6f},
 created = {2025-07-07T13:25:03.553Z},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-07-07T13:25:51.745Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively. © 2010 Macmillan Publishers Limited. All rights reserved.},
 bibtype = {article},
 author = {Qin, Junjie and Li, Ruiqiang and Raes, Jeroen and Arumugam, Manimozhiyan and Burgdorf, Kristoffer Solvsten and Manichanh, Chaysavanh and Nielsen, Trine and Pons, Nicolas and Levenez, Florence and Yamada, Takuji and Mende, Daniel R. and Li, Junhua and Xu, Junming and Li, Shaochuan and Li, Dongfang and Cao, Jianjun and Wang, Bo and Liang, Huiqing and Zheng, Huisong and Xie, Yinlong and Tap, Julien and Lepage, Patricia and Bertalan, Marcelo and Batto, Jean Michel and Hansen, Torben and Le Paslier, Denis and Linneberg, Allan and Nielsen, H. Bjørn and Pelletier, Eric and Renault, Pierre and Sicheritz-Ponten, Thomas and Turner, Keith and Zhu, Hongmei and Yu, Chang and Li, Shengting and Jian, Min and Zhou, Yan and Li, Yingrui and Zhang, Xiuqing and Li, Songgang and Qin, Nan and Yang, Huanming and Wang, Jian and Brunak, Søren and Doré, Joel and Guarner, Francisco and Kristiansen, Karsten and Pedersen, Oluf and Parkhill, Julian and Weissenbach, Jean and Bork, Peer and Ehrlich, S. Dusko and Wang, Jun and Antolin, Maria and Artiguenave, François and Blottiere, Hervé and Borruel, Natalia and Bruls, Thomas and Casellas, Francesc and Chervaux, Christian and Cultrone, Antonella and Delorme, Christine and Denariaz, Gérard and Dervyn, Rozenn and Forte, Miguel and Friss, Carsten and Van De Guchte, Maarten and Guedon, Eric and Haimet, Florence and Jamet, Alexandre and Juste, Catherine and Kaci, Ghalia and Kleerebezem, Michiel and Knol, Jan and Kristensen, Michel and Layec, Severine and Le Roux, Karine and Leclerc, Marion and Maguin, Emmanuelle and Melo Minardi, Raquel and Oozeer, Raish and Rescigno, Maria and Sanchez, Nicolas and Tims, Sebastian and Torrejon, Toni and Varela, Encarna and De Vos, Willem and Winogradsky, Yohanan and Zoetendal, Erwin},
 doi = {10.1038/nature08821},
 journal = {Nature},
 number = {7285}
}

To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively. © 2010 Macmillan Publishers Limited. All rights reserved.

@article{
 title = {Biological agent detection technologies},
 type = {article},
 year = {2009},
 keywords = {Barcoding,Biological agent,Detection,Identification,Sequencing},
 pages = {51-57},
 volume = {9},
 month = {5},
 id = {5bd6cf6a-17cd-32e9-bb02-c4a04036bf70},
 created = {2025-10-30T12:26:00.904Z},
 accessed = {2025-10-30},
 file_attached = {true},
 profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},
 group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},
 last_modified = {2025-10-30T12:26:14.257Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The challenge for first responders, physicians in the emergency room, public health personnel, as well as for food manufacturers, distributors and retailers is accurate and reliable identification of pathogenic agents and their corresponding diseases. This is the weakest point in biological agent detection capability today. There is intense research for new molecular detection technologies that could be used for very accurate detection of pathogens that would be a concern to first responders. These include the need for sensors for multiple applications as varied as understanding the ecology of pathogenic micro-organisms, forensics, environmental sampling for detect-to-treat applications, biological sensors for 'detect to warn' in infrastructure protection, responses to reports of 'suspicious powders', and customs and borders enforcement, to cite a few examples. The benefits of accurate detection include saving millions of dollars annually by reducing disruption of the workforce and the national economy and improving delivery of correct countermeasures to those who are most in need of the information to provide protective and/or response measures. © 2009 Blackwell Publishing Ltd.},
 bibtype = {article},
 author = {Jakupciak, John P. and Colwell, Rita R.},
 doi = {10.1111/J.1755-0998.2009.02632.X},
 journal = {Molecular Ecology Resources},
 number = {SUPPL. 1}
}

The challenge for first responders, physicians in the emergency room, public health personnel, as well as for food manufacturers, distributors and retailers is accurate and reliable identification of pathogenic agents and their corresponding diseases. This is the weakest point in biological agent detection capability today. There is intense research for new molecular detection technologies that could be used for very accurate detection of pathogens that would be a concern to first responders. These include the need for sensors for multiple applications as varied as understanding the ecology of pathogenic micro-organisms, forensics, environmental sampling for detect-to-treat applications, biological sensors for 'detect to warn' in infrastructure protection, responses to reports of 'suspicious powders', and customs and borders enforcement, to cite a few examples. The benefits of accurate detection include saving millions of dollars annually by reducing disruption of the workforce and the national economy and improving delivery of correct countermeasures to those who are most in need of the information to provide protective and/or response measures. © 2009 Blackwell Publishing Ltd.