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\n \n \n\n \n \n \n \n \n \n Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators.\n \n \n \n \n\n\n \n Kühnisch, J.; Theisen, S.; Dartsch, J.; Fritsche-Guenther, R.; Kirchner, M.; Obermayer, B.; Bauer, A.; Kahlert, A., K.; Rothe, M.; Beule, D.; Heuser, A.; Mertins, P.; Kirwan, J., A.; Berndt, N.; MacRae, C., A.; Hubner, N.; and Klaassen, S.\n\n\n \n\n\n\n Cardiovascular research, 119(18): 2902-2916. 12 2024.\n \n\n\n\n
\n\n\n\n \n \n![\"Prdm16](\"//bibbase.org/img/filetypes/pdf.svg\"\n\t "\\"Paper\\"\n\t")
Paper\n \n \n \n ![\"Prdm16](\"//bibbase.org/img/filetypes/link.svg\"\n\t "\\"Website\\"\n\t")
Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators},\n type = {article},\n year = {2024},\n keywords = {GC-MS,MCF,lipidomics},\n pages = {2902-2916},\n volume = {119},\n websites = {https://pubmed.ncbi.nlm.nih.gov/37842925/},\n month = {12},\n publisher = {Cardiovasc Res},\n day = {1},\n id = {891351cb-5516-3889-9233-73430e98a7c2},\n created = {2025-07-07T13:25:48.145Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:30.928Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1093/CVR/CVAD154},\n journal = {Cardiovascular research},\n number = {18}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Profiling Plasma Extracellular Vesicle Metabotypes and miRNAs: An Unobserved Clue for Predicting Relapse in Patients with Early-Stage NSCLC.\n \n \n \n \n\n\n \n Bafiti, V.; Thanou, E.; Ouzounis, S.; Kotsakis, A.; Georgoulias, V.; Lianidou, E.; Katsila, T.; and Markou, A.\n\n\n \n\n\n\n Cancers, 16(22): 3729. 11 2024.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
\n\n\n \n\n\n\n \n \n
Paper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{\n title = {Profiling Plasma Extracellular Vesicle Metabotypes and miRNAs: An Unobserved Clue for Predicting Relapse in Patients with Early-Stage NSCLC},\n type = {article},\n year = {2024},\n pages = {3729},\n volume = {16},\n websites = {https://www.mdpi.com/2072-6694/16/22/3729},\n month = {11},\n day = {5},\n id = {fb38fc0f-53d5-3798-a18d-62d2ec29b63b},\n created = {2025-07-07T13:25:48.482Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:31.249Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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>},\n bibtype = {article},\n author = {Bafiti, Vivi and Thanou, Eleni and Ouzounis, Sotiris and Kotsakis, Athanasios and Georgoulias, Vasilis and Lianidou, Evi and Katsila, Theodora and Markou, Athina},\n doi = {10.3390/cancers16223729},\n journal = {Cancers},\n number = {22}\n}\n\n
\n\n\nBackground 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.
\n\n \n\n \n \n \n \n \n \n Gut microbiota drives colon cancer risk associated with diet: a comparative analysis of meat-based and pesco-vegetarian diets.\n \n \n \n \n\n\n \n De Filippo, C.; Chioccioli, S.; Meriggi, N.; Troise, A., D.; Vitali, F.; Mejia Monroy, M.; Özsezen, S.; Tortora, K.; Balvay, A.; Maudet, C.; Naud, N.; Fouché, E.; Buisson, C.; Dupuy, J.; Bézirard, V.; Chevolleau, S.; Tondereau, V.; Theodorou, V.; Maslo, C.; Aubry, P.; Etienne, C.; Giovannelli, L.; Longo, V.; Scaloni, A.; Cavalieri, D.; Bouwman, J.; Pierre, F.; Gérard, P.; Guéraud, F.; and Caderni, G.\n\n\n \n\n\n\n Microbiome, 12(1): 180. 12 2024.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
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Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{\n title = {Gut microbiota drives colon cancer risk associated with diet: a comparative analysis of meat-based and pesco-vegetarian diets},\n type = {article},\n year = {2024},\n pages = {180},\n volume = {12},\n month = {12},\n day = {1},\n id = {ebfb7ffd-761b-3fd7-8f54-269d67bc7745},\n created = {2025-07-07T13:25:48.827Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:31.605Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1186/s40168-024-01900-2},\n journal = {Microbiome},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Sex specific gut-microbiota signatures of resilient and comorbid gut-brain phenotypes induced by early life stress.\n \n \n \n \n\n\n \n Wilmes, L.; Caputi, V.; Bastiaanssen, T., F.; Collins, J., M.; Crispie, F.; Cotter, P., D.; Dinan, T., G.; Cryan, J., F.; Clarke, G.; and O'Mahony, S., M.\n\n\n \n\n\n\n Neurobiology of Stress, 33. 11 2024.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Sex specific gut-microbiota signatures of resilient and comorbid gut-brain phenotypes induced by early life stress},\n type = {article},\n year = {2024},\n keywords = {Early life stress,IBS,Microbiota,Psychiatric comorbidities,Resilience,Sex differences,Visceral pain},\n volume = {33},\n month = {11},\n publisher = {Elsevier Inc.},\n day = {1},\n id = {50bcfc55-5243-3d54-8f84-420c8c903020},\n created = {2025-07-07T13:25:49.174Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:31.959Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1016/j.ynstr.2024.100686},\n journal = {Neurobiology of Stress}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Gut microbiota regulates stress responsivity via the circadian system.\n \n \n \n \n\n\n \n Tofani, G., S., S.; Leigh, S.; Gheorghe, C., E.; Bastiaanssen, T., F., S.; Wilmes, L.; Sen, P.; Clarke, G.; and Cryan, J., F.\n\n\n \n\n\n\n Cell Metabolism. 11 2024.\n \n\n\n\n
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\n\n\n@article{\n title = {Gut microbiota regulates stress responsivity via the circadian system},\n type = {article},\n year = {2024},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/39504963},\n month = {11},\n publisher = {Cell Press},\n day = {5},\n id = {168b8714-6605-32f3-8747-3db9f170d928},\n created = {2025-07-07T13:25:49.491Z},\n accessed = {2025-01-07},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:49.491Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1016/J.CMET.2024.10.003},\n journal = {Cell Metabolism}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Maternal high-fat diet-induced microbiota changes are associated with alterations in embryonic brain metabolites and adolescent behaviour.\n \n \n \n \n\n\n \n Ratsika, A.; Codagnone, M., G.; Bastiaanssen, T., F.; Hoffmann Sarda, F., A.; Lynch, C., M.; Ventura-Silva, A., P.; Rosell-Cardona, C.; Caputi, V.; Stanton, C.; Fülling, C.; Clarke, G.; and Cryan, J., F.\n\n\n \n\n\n\n Brain, Behavior, and Immunity, 121: 317-330. 10 2024.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Maternal high-fat diet-induced microbiota changes are associated with alterations in embryonic brain metabolites and adolescent behaviour},\n type = {article},\n year = {2024},\n keywords = {Anxiety-like behaviour,Glutamate,Maternal obesity,Microbiota-gut-brain axis,Neurodevelopment},\n pages = {317-330},\n volume = {121},\n month = {10},\n publisher = {Academic Press},\n day = {1},\n id = {d74a3fca-49c0-3e29-ba79-c24357a56f18},\n created = {2025-07-07T13:25:49.808Z},\n accessed = {2025-01-07},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:32.343Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1016/J.BBI.2024.07.020},\n journal = {Brain, Behavior, and Immunity}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Exercise mitigates a gut microbiota-mediated reduction in adult hippocampal neurogenesis and associated behaviours in rats.\n \n \n \n \n\n\n \n Nicolas, S.; Dohm-Hansen, S.; Lavelle, A.; Bastiaanssen, T., F.; English, J., A.; Cryan, J., F.; and Nolan, Y., M.\n\n\n \n\n\n\n Translational Psychiatry, 14(1). 12 2024.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Exercise mitigates a gut microbiota-mediated reduction in adult hippocampal neurogenesis and associated behaviours in rats},\n type = {article},\n year = {2024},\n volume = {14},\n month = {12},\n publisher = {Springer Nature},\n day = {1},\n id = {21a049be-0330-3ebf-aec1-d0e3d4e6faee},\n created = {2025-07-07T13:25:50.147Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:32.677Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1038/s41398-024-02904-0},\n journal = {Translational Psychiatry},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n 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.\n \n \n \n \n\n\n \n Toft-Bertelsen, T., L.; Andreassen, S., N.; Simonsen, A., H.; Hasselbalch, S., G.; and MacAulay, N.\n\n\n \n\n\n\n Brain Communications, 6(6). 2024.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n 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},\n type = {article},\n year = {2024},\n keywords = {CSF,iNPH,lipidomics,mass spectrometry},\n volume = {6},\n publisher = {Oxford University Press},\n id = {da8b8691-5354-377e-a8ba-d1a27617c0e9},\n created = {2025-07-07T13:25:50.473Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:33.031Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Toft-Bertelsen, Trine L. and Andreassen, Søren Norge and Simonsen, Anja Hviid and Hasselbalch, Steen Gregers and MacAulay, Nanna},\n doi = {10.1093/braincomms/fcae388},\n journal = {Brain Communications},\n number = {6}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid.\n \n \n \n \n\n\n \n Toft-Bertelsen, T., L.; Andreassen, S., N.; Norager, N., H.; Simonsen, A., H.; Hasselbalch, S., G.; Juhler, M.; and MacAulay, N.\n\n\n \n\n\n\n Biomolecules, 14(11). 11 2024.\n \n\n\n\n
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\n\n\n@article{\n title = {Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid},\n type = {article},\n year = {2024},\n keywords = {CSF,biomarkers,lipidomics,mass spectrometry},\n volume = {14},\n month = {11},\n publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},\n day = {1},\n id = {39f1e2dc-e7d1-31e2-8d1d-2dfcfaafa76a},\n created = {2025-07-07T13:25:50.861Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:33.370Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.3390/biom14111431},\n journal = {Biomolecules},\n number = {11}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Altitude-dependent agro-ecologies impact the microbiome diversity of scavenging indigenous chicken in Ethiopia.\n \n \n \n \n\n\n \n Glendinning, L.; Jia, X.; Kebede, A.; Oyola, S., O.; Park, J., E.; Park, W.; Assiri, A.; Holm, J., B.; Kristiansen, K.; Han, J.; and Hanotte, O.\n\n\n \n\n\n\n Microbiome, 12(1). 12 2024.\n \n\n\n\n
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\n\n\n@article{\n title = {Altitude-dependent agro-ecologies impact the microbiome diversity of scavenging indigenous chicken in Ethiopia},\n type = {article},\n year = {2024},\n keywords = {Agro-ecology,Chicken,Ethiopia,Metagenomics,Microbiota,Poultry},\n volume = {12},\n month = {12},\n publisher = {BioMed Central Ltd},\n day = {1},\n id = {ac9f111e-9936-3669-8dfd-c6763574f3a4},\n created = {2025-07-07T13:25:51.222Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:33.716Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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},\n bibtype = {article},\n 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},\n doi = {10.1186/s40168-024-01847-4},\n journal = {Microbiome},\n number = {1}\n}\n\n 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\n
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\n \n \n\n \n \n \n \n \n \n Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression.\n \n \n \n \n\n\n \n Juárez-Fernández, M.; Goikoetxea-Usandizaga, N.; Porras, D.; García-Mediavilla, M., V.; Bravo, M.; Serrano-Maciá, M.; Simón, J.; Delgado, T., C.; Lachiondo-Ortega, S.; Martínez-Flórez, S.; Lorenzo, Ó.; Rincón, M.; Varela-Rey, M.; Abecia, L.; Rodríguez, H.; Anguita, J.; Nistal, E.; Martínez-Chantar, M., L.; and Sánchez-Campos, S.\n\n\n \n\n\n\n Hepatology (Baltimore, Md.), 77(5): 1654-1669. 5 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression},\n type = {article},\n year = {2023},\n 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},\n pages = {1654-1669},\n volume = {77},\n websites = {https://pubmed.ncbi.nlm.nih.gov/35921199/},\n month = {5},\n publisher = {Hepatology},\n day = {1},\n id = {73fc4fff-f368-3560-bb2f-47e60905c1e1},\n created = {2025-07-07T13:25:41.308Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:41.308Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1002/HEP.32705},\n journal = {Hepatology (Baltimore, Md.)},\n number = {5}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Co-fermentation of non-Saccharomyces yeasts with Lactiplantibacillus plantarum FST 1.7 for the production of non-alcoholic beer.\n \n \n \n \n\n\n \n Nyhan, L.; Sahin, A., W.; and Arendt, E., K.\n\n\n \n\n\n\n European Food Research and Technology, 249(1): 167-181. 1 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {Co-fermentation of non-Saccharomyces yeasts with Lactiplantibacillus plantarum FST 1.7 for the production of non-alcoholic beer},\n type = {article},\n year = {2023},\n keywords = {Fermentate,MCF},\n pages = {167-181},\n volume = {249},\n websites = {https://link.springer.com/article/10.1007/s00217-022-04142-4},\n month = {1},\n publisher = {Springer Science and Business Media Deutschland GmbH},\n day = {1},\n id = {f28081cd-be9c-3f3c-875c-c03aec722348},\n created = {2025-07-07T13:25:41.730Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:25.249Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Nyhan, Laura and Sahin, Aylin W. and Arendt, Elke K.},\n doi = {10.1007/S00217-022-04142-4/FIGURES/3},\n journal = {European Food Research and Technology},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n In vitro and in silico assessment of probiotic and functional properties of Bacillus subtilis DE111®.\n \n \n \n \n\n\n \n Mazhar, S.; Khokhlova, E.; Colom, J.; Simon, A.; Deaton, J.; and Rea, K.\n\n\n \n\n\n\n Frontiers in microbiology, 13. 1 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {In vitro and in silico assessment of probiotic and functional properties of Bacillus subtilis DE111®},\n type = {article},\n year = {2023},\n keywords = {SCFA},\n volume = {13},\n websites = {https://pubmed.ncbi.nlm.nih.gov/36713219/},\n month = {1},\n publisher = {Front Microbiol},\n day = {13},\n id = {0f2a64e7-d3be-3e49-a47e-bb6eb5c929fc},\n created = {2025-07-07T13:25:42.067Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:42.067Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Mazhar, Shahneela and Khokhlova, Ekaterina and Colom, Joan and Simon, Annie and Deaton, John and Rea, Kieran},\n doi = {10.3389/FMICB.2022.1101144},\n journal = {Frontiers in microbiology}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients.\n \n \n \n \n\n\n \n Henriksen, H., H.; Marín de Mas, I.; Nielsen, L., K.; Krocker, J.; Stensballe, J.; Karvelsson, S., T.; Secher, N., H.; Rolfsson, Ó.; Wade, C., E.; and Johansson, P., I.\n\n\n \n\n\n\n International Journal of Molecular Sciences, 24(3). 2 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients},\n type = {article},\n year = {2023},\n keywords = {MCF,semi-polar},\n volume = {24},\n websites = {/pmc/articles/PMC9916682/,/pmc/articles/PMC9916682/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916682/},\n month = {2},\n publisher = {MDPI},\n day = {1},\n id = {c8ad95ce-f868-3a51-96d6-fa04859ba980},\n created = {2025-07-07T13:25:42.399Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:25.649Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.3390/IJMS24032257/S1},\n journal = {International Journal of Molecular Sciences},\n number = {3}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Hepatocyte mARC1 promotes fatty liver disease.\n \n \n \n \n\n\n \n Lewis, L., C.; Chen, L.; Hameed, L., S.; Kitchen, R., R.; Maroteau, C.; Nagarajan, S., R.; Norlin, J.; Daly, C., E.; Szczerbinska, I.; Hjuler, S., T.; Patel, R.; Livingstone, E., J.; Durrant, T., N.; Wondimu, E.; BasuRay, S.; Chandran, A.; Lee, W., H.; Hu, S.; Gilboa, B.; Grandi, M., E.; Toledo, E., M.; Erikat, A., H.; Hodson, L.; Haynes, W., G.; Pursell, N., W.; Coppieters, K.; Fleckner, J.; Howson, J., M.; Andersen, B.; and Ruby, M., A.\n\n\n \n\n\n\n JHEP reports : innovation in hepatology, 5(5). 5 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {Hepatocyte mARC1 promotes fatty liver disease},\n type = {article},\n year = {2023},\n keywords = {semi-polar},\n volume = {5},\n websites = {https://pubmed.ncbi.nlm.nih.gov/37122688/},\n month = {5},\n publisher = {JHEP Rep},\n day = {1},\n id = {9b9e0be4-e924-3394-b8cb-b525b3599767},\n created = {2025-07-07T13:25:42.775Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:26.014Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1016/J.JHEPR.2023.100693},\n journal = {JHEP reports : innovation in hepatology},\n number = {5}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Acute physiological effects following Bacillus subtilis DE111 oral ingestion - a randomised, double blinded, placebo-controlled study.\n \n \n \n \n\n\n \n Colom, J.; Freitas, D.; Simon, A.; Khokhlova, E.; Mazhar, S.; Buckley, M.; Phipps, C.; Deaton, J.; Brodkorb, A.; and Rea, K.\n\n\n \n\n\n\n Beneficial microbes, 14(1): 31-43. 2023.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Acute physiological effects following Bacillus subtilis DE111 oral ingestion - a randomised, double blinded, placebo-controlled study},\n type = {article},\n year = {2023},\n keywords = {semi-polar},\n pages = {31-43},\n volume = {14},\n websites = {https://pubmed.ncbi.nlm.nih.gov/36790091/},\n publisher = {Benef Microbes},\n id = {4a7b2590-3ec8-39f7-a742-60256c00797b},\n created = {2025-07-07T13:25:43.104Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:26.363Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.3920/BM2022.0081},\n journal = {Beneficial microbes},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Metabolomic profiles in relapsing-remitting and progressive multiple sclerosis compared to healthy controls: a five-year follow-up study.\n \n \n \n \n\n\n \n Shi, T.; Browne, R., W.; Tamaño-Blanco, M.; Jakimovski, D.; Weinstock-Guttman, B.; Zivadinov, R.; Ramanathan, M.; and Blair, R., H.\n\n\n \n\n\n\n Metabolomics : Official journal of the Metabolomic Society, 19(5). 5 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {Metabolomic profiles in relapsing-remitting and progressive multiple sclerosis compared to healthy controls: a five-year follow-up study},\n type = {article},\n year = {2023},\n keywords = {semi-polar},\n volume = {19},\n websites = {https://pubmed.ncbi.nlm.nih.gov/37079261/},\n month = {5},\n publisher = {Metabolomics},\n day = {1},\n id = {c3c89244-00f0-3eb2-9c68-53a7bdb7bc47},\n created = {2025-07-07T13:25:43.435Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:26.783Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1007/S11306-023-02010-0},\n journal = {Metabolomics : Official journal of the Metabolomic Society},\n number = {5}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Skin mucus metabolomics provides insights into the interplay between diet and wound in gilthead seabream (Sparus aurata).\n \n \n \n \n\n\n \n Albaladejo-Riad, N.; Espinosa-Ruiz, C.; Esteban, M., Á.; and Lazado, C., C.\n\n\n \n\n\n\n Fish & shellfish immunology, 134. 3 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {Skin mucus metabolomics provides insights into the interplay between diet and wound in gilthead seabream (Sparus aurata)},\n type = {article},\n year = {2023},\n keywords = {semi-polar},\n volume = {134},\n websites = {https://pubmed.ncbi.nlm.nih.gov/36746227/},\n month = {3},\n publisher = {Fish Shellfish Immunol},\n day = {1},\n id = {291d03ed-fc68-304e-b585-d821afcec792},\n created = {2025-07-07T13:25:43.796Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:27.212Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Albaladejo-Riad, Nora and Espinosa-Ruiz, Cristóbal and Esteban, María Ángeles and Lazado, Carlo C.},\n doi = {10.1016/J.FSI.2023.108590},\n journal = {Fish & shellfish immunology}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis.\n \n \n \n \n\n\n \n Grabrucker, S.; Marizzoni, M.; Silajžić, E.; Lopizzo, N.; Mombelli, E.; Nicolas, S.; Dohm-Hansen, S.; Scassellati, C.; Moretti, D., V.; Rosa, M.; Hoffmann, K.; Cryan, J., F.; O'Leary, O., F.; English, J., A.; Lavelle, A.; O'Neill, C.; Thuret, S.; Cattaneo, A.; and Nolan, Y., M.\n\n\n \n\n\n\n Brain, 146(12): 4916-4934. 12 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis},\n type = {article},\n year = {2023},\n keywords = {semi-polar},\n pages = {4916-4934},\n volume = {146},\n websites = {https://dx.doi.org/10.1093/brain/awad303},\n month = {12},\n publisher = {Oxford Academic},\n day = {1},\n id = {5b4d0d1a-1d59-3a85-812a-cb364b19bbe1},\n created = {2025-07-07T13:25:44.134Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:27.585Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1093/BRAIN/AWAD303},\n journal = {Brain},\n number = {12}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Gut microbes predominantly act as living beneficial partners rather than raw nutrients.\n \n \n \n \n\n\n \n da Silva Soares, N., F.; Quagliariello, A.; Yigitturk, S.; and Martino, M., E.\n\n\n \n\n\n\n Scientific Reports 2023 13:1, 13(1): 1-12. 7 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {Gut microbes predominantly act as living beneficial partners rather than raw nutrients},\n type = {article},\n year = {2023},\n keywords = {Microbiology,Physiology},\n pages = {1-12},\n volume = {13},\n websites = {https://www.nature.com/articles/s41598-023-38669-7},\n month = {7},\n publisher = {Nature Publishing Group},\n day = {24},\n id = {ad39e1bf-7658-36c0-a9cc-eb662151265c},\n created = {2025-07-07T13:25:44.448Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:27.963Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {da Silva Soares, Nuno Filipe and Quagliariello, Andrea and Yigitturk, Seren and Martino, Maria Elena},\n doi = {10.1038/s41598-023-38669-7},\n journal = {Scientific Reports 2023 13:1},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n NAD+ regulates nucleotide metabolism and genomic DNA replication.\n \n \n \n \n\n\n \n Munk, S., H., N.; Merchut-Maya, J., M.; Adelantado Rubio, A.; Hall, A.; Pappas, G.; Milletti, G.; Lee, M., H.; Johnsen, L., G.; Guldberg, P.; Bartek, J.; and Maya-Mendoza, A.\n\n\n \n\n\n\n Nature Cell Biology 2023 25:12, 25(12): 1774-1786. 11 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {NAD+ regulates nucleotide metabolism and genomic DNA replication},\n type = {article},\n year = {2023},\n keywords = {polar},\n pages = {1774-1786},\n volume = {25},\n websites = {https://www.nature.com/articles/s41556-023-01280-z},\n month = {11},\n publisher = {Nature Publishing Group},\n day = {13},\n id = {78495bc8-2f97-3e07-b54a-c772548f9d9b},\n created = {2025-07-07T13:25:44.780Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:28.321Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s41556-023-01280-z},\n journal = {Nature Cell Biology 2023 25:12},\n number = {12}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease.\n \n \n \n \n\n\n \n Berven, H.; Kverneng, S.; Sheard, E.; Søgnen, M.; Af Geijerstam, S., A.; Haugarvoll, K.; Skeie, G., O.; Dölle, C.; and Tzoulis, C.\n\n\n \n\n\n\n Nature Communications 2023 14:1, 14(1): 1-13. 11 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease},\n type = {article},\n year = {2023},\n keywords = {Drug safety,Parkinson's disease,Randomized controlled trials},\n pages = {1-13},\n volume = {14},\n websites = {https://www.nature.com/articles/s41467-023-43514-6},\n month = {11},\n publisher = {Nature Publishing Group},\n day = {28},\n id = {efeded12-b3af-363c-976e-a4f8694983bf},\n created = {2025-07-07T13:25:45.310Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:28.672Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s41467-023-43514-6},\n journal = {Nature Communications 2023 14:1},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Low-no-calorie sweeteners exert marked compound-specific impact on the human gut microbiota ex vivo.\n \n \n \n \n\n\n \n Van den Abbeele, P.; Poppe, J.; Deyaert, S.; Laurie, I.; Otto Gravert, T., K.; Abrahamsson, A.; Baudot, A.; Karnik, K.; and Risso, D.\n\n\n \n\n\n\n International journal of food sciences and nutrition, 74(5): 630-644. 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {Low-no-calorie sweeteners exert marked compound-specific impact on the human gut microbiota ex vivo},\n type = {article},\n year = {2023},\n 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},\n pages = {630-644},\n volume = {74},\n websites = {https://pubmed.ncbi.nlm.nih.gov/37537786/},\n publisher = {Int J Food Sci Nutr},\n id = {b3ae7917-7c69-36d3-bfcf-fe6c3cb766bb},\n created = {2025-07-07T13:25:45.693Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:45.693Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1080/09637486.2023.2240037},\n journal = {International journal of food sciences and nutrition},\n number = {5}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Oxygen Toxicity Causes Cyclic Damage by Destabilizing Specific Fe-S Cluster-Containing Protein Complexes.\n \n \n \n \n\n\n \n Baik, A., H.; Haribowo, A., G.; Chen, X.; Queliconi, B., B.; Barrios, A., M.; Garg, A.; Maishan, M.; Campos, A., R.; Matthay, M., A.; and Jain, I., H.\n\n\n \n\n\n\n Molecular cell, 83(6): 942. 3 2023.\n \n\n\n\n
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\n\n\n@article{\n title = {Oxygen Toxicity Causes Cyclic Damage by Destabilizing Specific Fe-S Cluster-Containing Protein Complexes},\n type = {article},\n year = {2023},\n keywords = {polar,semi-polar},\n pages = {942},\n volume = {83},\n websites = {/pmc/articles/PMC10148707/,/pmc/articles/PMC10148707/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148707/},\n month = {3},\n publisher = {NIH Public Access},\n day = {3},\n id = {e8b06420-f1bd-3b42-b821-f5eb653dccde},\n created = {2025-07-07T13:25:46.042Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:29.092Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1016/J.MOLCEL.2023.02.013},\n journal = {Molecular cell},\n number = {6}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Day-night fluctuations in choroid plexus transcriptomics and cerebrospinal fluid metabolomics.\n \n \n \n \n\n\n \n Edelbo, B., L.; Andreassen, S., N.; Steffensen, A., B.; and MacAulay, N.\n\n\n \n\n\n\n PNAS nexus, 2(8). 8 2023.\n \n\n\n\n
\n\n\n\n \n \nWebsite\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Day-night fluctuations in choroid plexus transcriptomics and cerebrospinal fluid metabolomics},\n type = {article},\n year = {2023},\n 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},\n volume = {2},\n websites = {https://pubmed.ncbi.nlm.nih.gov/37614671/},\n month = {8},\n publisher = {PNAS Nexus},\n day = {1},\n id = {d84f8c8f-baf8-3b58-ab88-5eb0724dffe7},\n created = {2025-07-07T13:25:46.371Z},\n accessed = {2024-04-12},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:46.371Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Edelbo, Beatriche Louise and Andreassen, Søren Norge and Steffensen, Annette Buur and MacAulay, Nanna},\n doi = {10.1093/PNASNEXUS/PGAD262},\n journal = {PNAS nexus},\n number = {8}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Age-associated deficits in social behaviour are microbiota-dependent.\n \n \n \n \n\n\n \n Cruz-Pereira, J., S.; Moloney, G., M.; Bastiaanssen, T., F.; Boscaini, S.; Fitzgerald, P.; Clarke, G.; and Cryan, J., F.\n\n\n \n\n\n\n Brain, Behavior, and Immunity, 110: 119-124. 5 2023.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Age-associated deficits in social behaviour are microbiota-dependent},\n type = {article},\n year = {2023},\n keywords = {Aging,Metabolites,Microbiome,Social behaviour},\n pages = {119-124},\n volume = {110},\n month = {5},\n publisher = {Academic Press},\n day = {1},\n id = {e6c05544-746b-3a2e-8233-93c9a111aef7},\n created = {2025-07-07T13:25:46.768Z},\n accessed = {2025-01-07},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:29.531Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1016/J.BBI.2023.02.008},\n journal = {Brain, Behavior, and Immunity}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population.\n \n \n \n \n\n\n \n Berding, K.; Bastiaanssen, T., F.; Moloney, G., M.; Boscaini, S.; Strain, C., R.; Anesi, A.; Long-Smith, C.; Mattivi, F.; Stanton, C.; Clarke, G.; Dinan, T., G.; and Cryan, J., F.\n\n\n \n\n\n\n Molecular Psychiatry, 28(2): 601-610. 2 2023.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population},\n type = {article},\n year = {2023},\n pages = {601-610},\n volume = {28},\n month = {2},\n publisher = {Springer Nature},\n day = {1},\n id = {47679c57-7cd2-3d82-ab8d-4f2935872de9},\n created = {2025-07-07T13:25:47.115Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:29.887Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1038/s41380-022-01817-y},\n journal = {Molecular Psychiatry},\n number = {2}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Distinct Cerebrospinal Fluid Lipid Signature in Patients with Subarachnoid Hemorrhage-Induced Hydrocephalus.\n \n \n \n \n\n\n \n Toft-Bertelsen, T., L.; Andreassen, S., N.; Rostgaard, N.; Olsen, M., H.; Norager, N., H.; Capion, T.; Juhler, M.; and MacAulay, N.\n\n\n \n\n\n\n Biomedicines, 11(9). 9 2023.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Distinct Cerebrospinal Fluid Lipid Signature in Patients with Subarachnoid Hemorrhage-Induced Hydrocephalus},\n type = {article},\n year = {2023},\n keywords = {SAH,cerebrospinal fluid,lipidomics,mass spectrometry,posthemorrhagic hydrocephalus},\n volume = {11},\n month = {9},\n publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},\n day = {1},\n id = {7e76599f-0d8b-396c-be29-5c44e1a2c626},\n created = {2025-07-07T13:25:47.444Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:30.208Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.3390/biomedicines11092360},\n journal = {Biomedicines},\n number = {9}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Obstructive sleep apnea was associated with the human gut microbiota composition and functional potential in the population-based Swedish CardioPulmonary bioImage Study (SCAPIS).\n \n \n \n \n\n\n \n Baldanzi, G.; Sayols-Baixeras, S.; Theorell-Haglöw, J.; Dekkers, K., F.; Hammar, U.; Nguyen, D.; Lin, Y.; Ahmad, S.; Holm, J., B.; Nielsen, H., B.; Brunkwall, L.; Benedict, C.; Cedernaes, J.; Koskiniemi, S.; Phillipson, M.; Lind, L.; Sundström, J.; Bergström, G.; Engström, G.; Smith, J., G.; Orho-Melander, M.; Ärnlöv, J.; Kennedy, B.; Lindberg, E.; and Fall, T.\n\n\n \n\n\n\n Chest, (April). 2023.\n \n\n\n\n
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\n\n\n\n@article{\n title = {Obstructive sleep apnea was associated with the human gut microbiota composition and functional potential in the population-based Swedish CardioPulmonary bioImage Study (SCAPIS)},\n type = {article},\n year = {2023},\n websites = {https://doi.org/10.1016/j.chest.2023.03.010},\n publisher = {The Author(s)},\n id = {719e01f4-db56-378f-9373-59c10ca601d8},\n created = {2025-07-07T13:25:47.776Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:30.582Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n bibtype = {article},\n 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},\n doi = {10.1016/j.chest.2023.03.010},\n journal = {Chest},\n number = {April}\n}\n\n
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\n \n \n\n \n \n \n \n \n \n Increased circulating butyrate and ursodeoxycholate during probiotic intervention in humans with type 2 diabetes.\n \n \n \n \n\n\n \n McMurdie, P., J.; Stoeva, M., K.; Justice, N.; Nemchek, M.; Sieber, C., M.; Tyagi, S.; Gines, J.; Skennerton, C., T.; Souza, M.; Kolterman, O.; and Eid, J.\n\n\n \n\n\n\n BMC Microbiology, 22(1): 1-18. 12 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {Increased circulating butyrate and ursodeoxycholate during probiotic intervention in humans with type 2 diabetes},\n type = {article},\n year = {2022},\n keywords = {semi-polar},\n pages = {1-18},\n volume = {22},\n websites = {https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-021-02415-8},\n month = {12},\n publisher = {BioMed Central Ltd},\n day = {1},\n id = {39254efd-5e47-3f87-82f9-372835ca0128},\n created = {2025-07-07T13:25:37.073Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:20.948Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1186/S12866-021-02415-8/FIGURES/5},\n journal = {BMC Microbiology},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Human milk oligosaccharide-sharing by a consortium of infant derived Bifidobacterium species.\n \n \n \n \n\n\n \n Walsh, C.; Lane, J., A.; van Sinderen, D.; and Hickey, R., M.\n\n\n \n\n\n\n Scientific Reports 2022 12:1, 12(1): 1-14. 3 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {Human milk oligosaccharide-sharing by a consortium of infant derived Bifidobacterium species},\n type = {article},\n year = {2022},\n keywords = {MCF,Spent media},\n pages = {1-14},\n volume = {12},\n websites = {https://www.nature.com/articles/s41598-022-07904-y},\n month = {3},\n publisher = {Nature Publishing Group},\n day = {9},\n id = {f3a15f54-ed0b-3300-8208-b3f27f9ae90f},\n created = {2025-07-07T13:25:37.393Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:21.288Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Walsh, Clodagh and Lane, Jonathan A. and van Sinderen, Douwe and Hickey, Rita M.},\n doi = {10.1038/s41598-022-07904-y},\n journal = {Scientific Reports 2022 12:1},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n CmP Signaling Network Leads to Identification of Prognostic Biomarkers for Triple-Negative Breast Cancer in Caucasian Women.\n \n \n \n \n\n\n \n Abou-Fadel, J.; Bhalli, M.; Grajeda, B.; and Zhang, J.\n\n\n \n\n\n\n Genetic testing and molecular biomarkers, 26(4): 198-219. 4 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {CmP Signaling Network Leads to Identification of Prognostic Biomarkers for Triple-Negative Breast Cancer in Caucasian Women},\n type = {article},\n year = {2022},\n 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},\n pages = {198-219},\n volume = {26},\n websites = {https://pubmed.ncbi.nlm.nih.gov/35481969/},\n month = {4},\n publisher = {Genet Test Mol Biomarkers},\n day = {1},\n id = {cd32ccab-19f2-3ca6-b6b5-3d64e487d30b},\n created = {2025-07-07T13:25:37.799Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:37.799Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Abou-Fadel, Johnathan and Bhalli, Muaz and Grajeda, Brian and Zhang, Jun},\n doi = {10.1089/GTMB.2021.0221},\n journal = {Genetic testing and molecular biomarkers},\n number = {4}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Human milk oligosaccharides induce acute yet reversible compositional changes in the gut microbiota of conventional mice linked to a reduction of butyrate levels.\n \n \n \n \n\n\n \n Holst, A., Q.; Jois, H.; Laursen, M., F.; Sommer, M., O., A.; Licht, T., R.; and Bahl, M., I.\n\n\n \n\n\n\n microLife, 3. 6 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {Human milk oligosaccharides induce acute yet reversible compositional changes in the gut microbiota of conventional mice linked to a reduction of butyrate levels},\n type = {article},\n year = {2022},\n 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},\n volume = {3},\n websites = {https://pubmed.ncbi.nlm.nih.gov/37223362/},\n month = {6},\n publisher = {Microlife},\n day = {22},\n id = {fc01237f-1922-3157-968d-bf54e391e768},\n created = {2025-07-07T13:25:38.163Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:21.794Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Holst, Andrea Qvortrup and Jois, Harshitha and Laursen, Martin Frederik and Sommer, Morten O A and Licht, Tine Rask and Bahl, Martin Iain},\n doi = {10.1093/FEMSML/UQAC006},\n journal = {microLife}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Metabolic systems analysis identifies a novel mechanism contributing to shock in patients with endotheliopathy of trauma (EoT) involving thromboxane A2 and LTC4.\n \n \n \n \n\n\n \n Henriksen, H., H.; Marín de Mas, I.; Herand, H.; Krocker, J.; Wade, C., E.; and Johansson, P., I.\n\n\n \n\n\n\n Matrix biology plus, 15. 8 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {Metabolic systems analysis identifies a novel mechanism contributing to shock in patients with endotheliopathy of trauma (EoT) involving thromboxane A2 and LTC4},\n type = {article},\n year = {2022},\n keywords = {MCF,RP,semi-polar},\n volume = {15},\n websites = {https://pubmed.ncbi.nlm.nih.gov/35813244/},\n month = {8},\n publisher = {Matrix Biol Plus},\n day = {1},\n id = {c8c5c4ca-1d5d-3a93-8611-56d6545eb259},\n created = {2025-07-07T13:25:38.571Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:22.156Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Henriksen, Hanne H. and Marín de Mas, Igor and Herand, Helena and Krocker, Joseph and Wade, Charles E. and Johansson, Pär I.},\n doi = {10.1016/J.MBPLUS.2022.100115},\n journal = {Matrix biology plus}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Targeted plasma metabolomics in resuscitated comatose out-of-hospital cardiac arrest patients.\n \n \n \n \n\n\n \n Paulin Beske, R.; Henriksen, H., H.; Obling, L.; Kjærgaard, J.; Bro-Jeppesen, J.; Nielsen, N.; Johansson, P., I.; and Hassager, C.\n\n\n \n\n\n\n Resuscitation, 179: 163-171. 10 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {Targeted plasma metabolomics in resuscitated comatose out-of-hospital cardiac arrest patients},\n type = {article},\n year = {2022},\n keywords = {MCF,semi-polar},\n pages = {163-171},\n volume = {179},\n websites = {https://pubmed.ncbi.nlm.nih.gov/35753507/},\n month = {10},\n publisher = {Resuscitation},\n day = {1},\n id = {500ca218-e6e0-31ff-8705-3676884fe4d6},\n created = {2025-07-07T13:25:38.920Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:22.535Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1016/J.RESUSCITATION.2022.06.010},\n journal = {Resuscitation}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects.\n \n \n \n \n\n\n \n Cortellino, S.; Raveane, A.; Chiodoni, C.; Delfanti, G.; Pisati, F.; Spagnolo, V.; Visco, E.; Fragale, G.; Ferrante, F.; Magni, S.; Iannelli, F.; Zanardi, F.; Casorati, G.; Bertolini, F.; Dellabona, P.; Colombo, M., P.; Tripodo, C.; and Longo, V., D.\n\n\n \n\n\n\n Cell reports, 40(8). 8 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects},\n type = {article},\n year = {2022},\n keywords = {polar},\n volume = {40},\n websites = {https://pubmed.ncbi.nlm.nih.gov/36001966/},\n month = {8},\n publisher = {Cell Rep},\n day = {23},\n id = {ae6559f3-decf-3154-9a38-324eb150e02d},\n created = {2025-07-07T13:25:39.262Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:22.921Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1016/J.CELREP.2022.111256},\n journal = {Cell reports},\n number = {8}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Dysregulated Sulfide Metabolism in Multiple Sclerosis: Serum and Vascular Endothelial Inflammatory Responses.\n \n \n \n \n\n\n \n Veerareddy, P.; Dao, N.; Yun, J., W.; Stokes, K., Y.; Disbrow, E.; Kevil, C., G.; Cvek, U.; Trutschl, M.; Kilgore, P.; Ramanathan, M.; Zivadinov, R.; and Alexander, J., S.\n\n\n \n\n\n\n Pathophysiology, 29(3): 570. 9 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {Dysregulated Sulfide Metabolism in Multiple Sclerosis: Serum and Vascular Endothelial Inflammatory Responses},\n type = {article},\n year = {2022},\n keywords = {semi-polar},\n pages = {570},\n volume = {29},\n websites = {/pmc/articles/PMC9502521/,/pmc/articles/PMC9502521/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502521/},\n month = {9},\n publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},\n day = {1},\n id = {93561bf9-1579-3f40-8b18-677381a92934},\n created = {2025-07-07T13:25:39.606Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:23.270Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.3390/PATHOPHYSIOLOGY29030044},\n journal = {Pathophysiology},\n number = {3}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient: a case report.\n \n \n \n \n\n\n \n Wei, S.; Jespersen, M., L.; Baunwall, S., M., D.; Myers, P., N.; Smith, E., M.; Dahlerup, J., F.; Rasmussen, S.; Nielsen, H., B.; Licht, T., R.; Bahl, M., I.; and Hvas, C., L.\n\n\n \n\n\n\n Microbiome, 10(1): 1-14. 12 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient: a case report},\n type = {article},\n year = {2022},\n keywords = {SCFA},\n pages = {1-14},\n volume = {10},\n websites = {https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01394-w},\n month = {12},\n publisher = {BioMed Central Ltd},\n day = {1},\n id = {a02fa5ca-0b1d-3215-ae27-ac18a46e2f8a},\n created = {2025-07-07T13:25:39.949Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:23.711Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.]},\n bibtype = {article},\n 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},\n doi = {10.1186/S40168-022-01394-W/FIGURES/4},\n journal = {Microbiome},\n number = {1}\n}\n\n 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.]\n
\n\n\n\n \n\n \n \n \n \n \n \n The circulating plasma metabolome of Neoparamoeba perurans-infected Atlantic salmon (Salmo salar).\n \n \n \n \n\n\n \n Lazado, C., C.; Breiland, M., W.; Furtado, F.; Burgerhout, E.; and Strand, D.\n\n\n \n\n\n\n Microbial pathogenesis, 166. 5 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {The circulating plasma metabolome of Neoparamoeba perurans-infected Atlantic salmon (Salmo salar)},\n type = {article},\n year = {2022},\n keywords = {semi-polar},\n volume = {166},\n websites = {https://pubmed.ncbi.nlm.nih.gov/35472502/},\n month = {5},\n publisher = {Microb Pathog},\n day = {1},\n id = {c875ee5f-3657-3aab-84a5-a8bafefbb79f},\n created = {2025-07-07T13:25:40.302Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:24.075Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Lazado, Carlo C. and Breiland, Mette W. and Furtado, Francisco and Burgerhout, Erik and Strand, David},\n doi = {10.1016/J.MICPATH.2022.105553},\n journal = {Microbial pathogenesis}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Prebiotic supplementation modulates selective effects of stress on behavior and brain metabolome in aged mice.\n \n \n \n \n\n\n \n Cruz-Pereira, J., S.; Moloney, G., M.; Bastiaanssen, T., F.; Boscaini, S.; Tofani, G.; Borras-Bisa, J.; van de Wouw, M.; Fitzgerald, P.; Dinan, T., G.; Clarke, G.; and Cryan, J., F.\n\n\n \n\n\n\n Neurobiology of Stress, 21. 11 2022.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Prebiotic supplementation modulates selective effects of stress on behavior and brain metabolome in aged mice},\n type = {article},\n year = {2022},\n keywords = {Aging,Diet,Metabolome,Prebiotics,Stress},\n volume = {21},\n month = {11},\n publisher = {Elsevier Inc.},\n day = {1},\n id = {c1723eee-baa1-3796-8f13-d86e5a7530e3},\n created = {2025-07-07T13:25:40.643Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:24.432Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1016/j.ynstr.2022.100501},\n journal = {Neurobiology of Stress}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n An online atlas of human plasma metabolite signatures of gut microbiome composition.\n \n \n \n \n\n\n \n Dekkers, K., F.; Sayols-Baixeras, S.; Baldanzi, G.; Nowak, C.; Hammar, U.; Nguyen, D.; Varotsis, G.; Brunkwall, L.; Nielsen, N.; Eklund, A., C.; Bak Holm, J.; Nielsen, H., B.; Ottosson, F.; Lin, Y.; Ahmad, S.; Lind, L.; Sundström, J.; Engström, G.; Smith, J., G.; Ärnlöv, J.; Orho-Melander, M.; and Fall, T.\n\n\n \n\n\n\n Nature Communications, 13(1): 5370. 9 2022.\n \n\n\n\n
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\n\n\n@article{\n title = {An online atlas of human plasma metabolite signatures of gut microbiome composition},\n type = {article},\n year = {2022},\n pages = {5370},\n volume = {13},\n 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},\n month = {9},\n publisher = {Springer US},\n day = {23},\n id = {00a1d48e-aa5e-36d5-b74a-d5a61caf6bf0},\n created = {2025-07-07T13:25:40.970Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:24.818Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s41467-022-33050-0},\n journal = {Nature Communications},\n number = {1}\n}\n\n 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.\n
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\n \n \n\n \n \n \n \n \n \n Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut.\n \n \n \n \n\n\n \n Laursen, M., F.; Sakanaka, M.; von Burg, N.; Mörbe, U.; Andersen, D.; Moll, J., M.; Pekmez, C., T.; Rivollier, A.; Michaelsen, K., F.; Mølgaard, C.; Lind, M., V.; Dragsted, L., O.; Katayama, T.; Frandsen, H., L.; Vinggaard, A., M.; Bahl, M., I.; Brix, S.; Agace, W.; Licht, T., R.; and Roager, H., M.\n\n\n \n\n\n\n Nature Microbiology 2021 6:11, 6(11): 1367-1382. 10 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut},\n type = {article},\n year = {2021},\n keywords = {Enzymes,Metabolomics,Microbial ecology,Microbiome},\n pages = {1367-1382},\n volume = {6},\n websites = {https://www.nature.com/articles/s41564-021-00970-4},\n month = {10},\n publisher = {Nature Publishing Group},\n day = {21},\n id = {0dffff8a-fb11-37a6-a2ec-88d3742a6f24},\n created = {2025-07-07T13:25:30.140Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:15.771Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1038/s41564-021-00970-4},\n journal = {Nature Microbiology 2021 6:11},\n number = {11}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n Crowding reshapes the mucosal but not the systemic response repertoires of Atlantic salmon to peracetic acid.\n \n \n \n\n\n \n Lazado, C., C.; Sveen, L., R.; Soleng, M.; Pedersen, L., F.; and Timmerhaus, G.\n\n\n \n\n\n\n Aquaculture, 531: 735830. 1 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Crowding reshapes the mucosal but not the systemic response repertoires of Atlantic salmon to peracetic acid},\n type = {article},\n year = {2021},\n keywords = {Amoebic gill disease,Crowding stress,Hydrogen peroxide,Mucosal health,Oxidative stress,Peracetic acid},\n pages = {735830},\n volume = {531},\n month = {1},\n publisher = {Elsevier},\n day = {30},\n id = {585309cf-42de-34c7-bbfb-b95f494c3620},\n created = {2025-07-07T13:25:30.458Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:30.458Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Lazado, Carlo C. and Sveen, Lene R. and Soleng, Malene and Pedersen, Lars Flemming and Timmerhaus, Gerrit},\n doi = {10.1016/J.AQUACULTURE.2020.735830},\n journal = {Aquaculture}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Impact of dietary propionate on fructose-induced changes in lipid metabolism, gut microbiota and short-chain fatty acids in mice.\n \n \n \n \n\n\n \n Brütting, C.; Lara Bisch, M.; Brandsch, C.; Hirche, F.; and Stangl, G., I.\n\n\n \n\n\n\n International Journal of Food Sciences and Nutrition, 72(2): 160-173. 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Impact of dietary propionate on fructose-induced changes in lipid metabolism, gut microbiota and short-chain fatty acids in mice},\n type = {article},\n year = {2021},\n keywords = {SCFA},\n pages = {160-173},\n volume = {72},\n websites = {https://www.tandfonline.com/doi/abs/10.1080/09637486.2020.1773415},\n publisher = {Taylor & Francis},\n id = {8a0c9adc-f256-353d-8222-7663d785c1cd},\n created = {2025-07-07T13:25:30.771Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:30.771Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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...},\n bibtype = {article},\n author = {Brütting, Christine and Lara Bisch, Milena and Brandsch, Corinna and Hirche, Frank and Stangl, Gabriele I.},\n doi = {10.1080/09637486.2020.1773415},\n journal = {International Journal of Food Sciences and Nutrition},\n number = {2}\n}\n\n 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...\n
\n\n\n\n \n\n \n \n \n \n \n \n Publisher Correction: Inhibition of succinate dehydrogenase activity impairs human T cell activation and function.\n \n \n \n \n\n\n \n Nastasi, C.; Willerlev-Olsen, A.; Dalhoff, K.; Ford, S., L.; Gadsbøll, A., S., Ø.; Buus, T., B.; Gluud, M.; Danielsen, M.; Litman, T.; Bonefeld, C., M.; Geisler, C.; Ødum, N.; and Woetmann, A.\n\n\n \n\n\n\n Scientific reports, 11(1). 12 2021.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Publisher Correction: Inhibition of succinate dehydrogenase activity impairs human T cell activation and function},\n type = {article},\n year = {2021},\n keywords = {polar},\n volume = {11},\n websites = {https://pubmed.ncbi.nlm.nih.gov/33875757/},\n month = {12},\n publisher = {Sci Rep},\n day = {1},\n id = {24aa7391-76bb-38ab-a4d3-f2f8f0460bcc},\n created = {2025-07-07T13:25:31.129Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:16.215Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.”},\n bibtype = {article},\n 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},\n doi = {10.1038/S41598-021-88184-W},\n journal = {Scientific reports},\n number = {1}\n}\n\n 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.”\n
\n\n\n\n \n\n \n \n \n \n \n \n Inhibition of succinate dehydrogenase activity impairs human T cell activation and function.\n \n \n \n \n\n\n \n Nastasi, C.; Willerlev-Olsen, A.; Dalhoff, K.; Ford, S., L.; Gadsbøll, A., S., Ø.; Buus, T., B.; Gluud, M.; Danielsen, M.; Litman, T.; Bonefeld, C., M.; Geisler, C.; Ødum, N.; and Woetmann, A.\n\n\n \n\n\n\n Scientific Reports, 11(1): 1458. 12 2021.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n
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Paper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n\n
\n\n\n@article{\n title = {Inhibition of succinate dehydrogenase activity impairs human T cell activation and function},\n type = {article},\n year = {2021},\n pages = {1458},\n volume = {11},\n websites = {/pmc/articles/PMC7809054/,/pmc/articles/PMC7809054/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809054/},\n month = {12},\n publisher = {Nature Publishing Group},\n day = {1},\n id = {fbc304f3-7a1a-39d5-b008-e83155f051a3},\n created = {2025-07-07T13:25:31.480Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:16.568Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/S41598-020-80933-7},\n journal = {Scientific Reports},\n number = {1},\n keywords = {polar}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Cyclic CMP and cyclic UMP mediate bacterial immunity against phages.\n \n \n \n \n\n\n \n Tal, N.; Morehouse, B., R.; Millman, A.; Stokar-Avihail, A.; Avraham, C.; Fedorenko, T.; Yirmiya, E.; Herbst, E.; Brandis, A.; Mehlman, T.; Oppenheimer-Shaanan, Y.; Keszei, A., F.; Shao, S.; Amitai, G.; Kranzusch, P., J.; and Sorek, R.\n\n\n \n\n\n\n Cell, 184(23): 5728-5739.e16. 11 2021.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Cyclic CMP and cyclic UMP mediate bacterial immunity against phages},\n type = {article},\n year = {2021},\n keywords = {nucelotides,polar},\n pages = {5728-5739.e16},\n volume = {184},\n 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},\n month = {11},\n publisher = {Elsevier B.V.},\n day = {11},\n id = {7f9b4b6e-3ee1-3420-ba72-bf039b4a6f06},\n created = {2025-07-07T13:25:31.839Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:16.904Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1016/j.cell.2021.09.031},\n journal = {Cell},\n number = {23}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium.\n \n \n \n \n\n\n \n Thyrsted, J.; Storgaard, J.; Blay-Cadanet, J.; Heinz, A.; Thielke, A., L.; Crotta, S.; de Paoli, F.; Olagnier, D.; Wack, A.; Hiller, K.; Hansen, A., L.; and Holm, C., K.\n\n\n \n\n\n\n iScience, 24(11). 11 2021.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium},\n type = {article},\n year = {2021},\n keywords = {Immune response,Metabolomics,Virology},\n volume = {24},\n 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},\n month = {11},\n publisher = {Elsevier Inc.},\n day = {19},\n id = {03764b58-c469-33bd-b86e-0faea19d0fc2},\n created = {2025-07-07T13:25:32.184Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:17.262Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1016/j.isci.2021.103300},\n journal = {iScience},\n number = {11}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Non-canonical glutamine transamination sustains efferocytosis by coupling redox buffering to oxidative phosphorylation.\n \n \n \n \n\n\n \n Merlin, J.; Ivanov, S.; Dumont, A.; Sergushichev, A.; Gall, J.; Stunault, M.; Ayrault, M.; Vaillant, N.; Castiglione, A.; Swain, A.; Orange, F.; Gallerand, A.; Berton, T.; Martin, J., C.; Carobbio, S.; Masson, J.; Gaisler-Salomon, I.; Maechler, P.; Rayport, S.; Sluimer, J., C.; Biessen, E., A.; Guinamard, R., R.; Gautier, E., L.; Thorp, E., B.; Artyomov, M., N.; and Yvan-Charvet, L.\n\n\n \n\n\n\n Nature Metabolism 2021 3:10, 3(10): 1313-1326. 10 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Non-canonical glutamine transamination sustains efferocytosis by coupling redox buffering to oxidative phosphorylation},\n type = {article},\n year = {2021},\n keywords = {Atherosclerosis,Chronic inflammation,Metabolic diseases,Phagocytes},\n pages = {1313-1326},\n volume = {3},\n websites = {https://www.nature.com/articles/s42255-021-00471-y},\n month = {10},\n publisher = {Nature Publishing Group},\n day = {14},\n id = {4da999c6-8149-31c7-9fe4-47801cb4f8b8},\n created = {2025-07-07T13:25:32.511Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:32.511Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s42255-021-00471-y},\n journal = {Nature Metabolism 2021 3:10},\n number = {10}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Host Stress Signals Stimulate Pneumococcal Transition from Colonization to Dissemination into the Lungs.\n \n \n \n \n\n\n \n Alghofaili, F.; Najmuldeen, H.; Kareem, B., O.; Shlla, B.; Fernandes, V., E.; Danielsen, M.; Ketley, J., M.; Freestone, P.; and Yesilkaya, H.\n\n\n \n\n\n\n mBio, 12(6). 12 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Host Stress Signals Stimulate Pneumococcal Transition from Colonization to Dissemination into the Lungs},\n type = {article},\n year = {2021},\n keywords = {MCF},\n volume = {12},\n websites = {https://pubmed.ncbi.nlm.nih.gov/34696596/},\n month = {12},\n publisher = {mBio},\n day = {1},\n id = {a2d4f572-0989-3e5a-99f9-7c68dd26e2af},\n created = {2025-07-07T13:25:32.840Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:32.840Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1128/MBIO.02569-21},\n journal = {mBio},\n number = {6}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome.\n \n \n \n \n\n\n \n Iribarren, C.; Magnusson, M., K.; Vigsnæs, L., K.; Aziz, I.; Amundsen, I., D.; Šuligoj, T.; Juge, N.; Patel, P.; Sapnara, M.; Johnsen, L.; Sørensen, N.; Sundin, J.; Törnblom, H.; Simrén, M.; and Öhman, L.\n\n\n \n\n\n\n Nutrients, 13(11). 11 2021.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome},\n type = {article},\n year = {2021},\n keywords = {semi-polar},\n volume = {13},\n websites = {https://pubmed.ncbi.nlm.nih.gov/34836092/},\n month = {11},\n publisher = {Nutrients},\n day = {1},\n id = {1ebf521d-ed7e-3553-b841-d9e13a7638ed},\n created = {2025-07-07T13:25:33.222Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:17.811Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.3390/NU13113836},\n journal = {Nutrients},\n number = {11}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Effector-mediated membrane disruption controls cell death in CBASS antiphage defense.\n \n \n \n \n\n\n \n Duncan-Lowey, B.; McNamara-Bordewick, N., K.; Tal, N.; Sorek, R.; and Kranzusch, P., J.\n\n\n \n\n\n\n Molecular cell, 81(24): 5039-5051.e5. 12 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Effector-mediated membrane disruption controls cell death in CBASS antiphage defense},\n type = {article},\n year = {2021},\n keywords = {nucelotides,polar},\n pages = {5039-5051.e5},\n volume = {81},\n websites = {https://pubmed.ncbi.nlm.nih.gov/34784509/},\n month = {12},\n publisher = {Mol Cell},\n day = {16},\n id = {52da013f-cd64-3668-ba6c-d58ce6c8ba56},\n created = {2025-07-07T13:25:33.544Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:18.200Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Duncan-Lowey, Brianna and McNamara-Bordewick, Nora K. and Tal, Nitzan and Sorek, Rotem and Kranzusch, Philip J.},\n doi = {10.1016/J.MOLCEL.2021.10.020},\n journal = {Molecular cell},\n number = {24}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer.\n \n \n \n \n\n\n \n Luu, M.; Riester, Z.; Baldrich, A.; Reichardt, N.; Yuille, S.; Busetti, A.; Klein, M.; Wempe, A.; Leister, H.; Raifer, H.; Picard, F.; Muhammad, K.; Ohl, K.; Romero, R.; Fischer, F.; Bauer, C., A.; Huber, M.; Gress, T., M.; Lauth, M.; Danhof, S.; Bopp, T.; Nerreter, T.; Mulder, I., E.; Steinhoff, U.; Hudecek, M.; and Visekruna, A.\n\n\n \n\n\n\n Nature communications, 12(1). 12 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer},\n type = {article},\n year = {2021},\n keywords = {SCFA},\n volume = {12},\n websites = {https://pubmed.ncbi.nlm.nih.gov/34210970/},\n month = {12},\n publisher = {Nat Commun},\n day = {1},\n id = {5aa65f60-a638-305e-99ce-ff6c628cb40d},\n created = {2025-07-07T13:25:33.884Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:18.529Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/S41467-021-24331-1},\n journal = {Nature communications},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense.\n \n \n \n \n\n\n \n Govande, A., A.; Duncan-Lowey, B.; Eaglesham, J., B.; Whiteley, A., T.; and Kranzusch, P., J.\n\n\n \n\n\n\n Cell Reports, 35(9): 109206. 6 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense},\n type = {article},\n year = {2021},\n keywords = {nucleotides,polar},\n pages = {109206},\n volume = {35},\n month = {6},\n publisher = {Cell Press},\n day = {1},\n id = {e8119c6a-9ef0-3fd9-aade-ceadf9d53d42},\n created = {2025-07-07T13:25:34.222Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:18.901Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Govande, Apurva A. and Duncan-Lowey, Brianna and Eaglesham, James B. and Whiteley, Aaron T. and Kranzusch, Philip J.},\n doi = {10.1016/J.CELREP.2021.109206},\n journal = {Cell Reports},\n number = {9}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Identification of potential citrate metabolism pathways in carnobacterium maltaromaticum.\n \n \n \n \n\n\n \n Li, H.; Ramia, N., E.; Borges, F.; Revol-Junelles, A., M.; Vogensen, F., K.; and Leisner, J., J.\n\n\n \n\n\n\n Microorganisms, 9(10): 2169. 10 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Identification of potential citrate metabolism pathways in carnobacterium maltaromaticum},\n type = {article},\n year = {2021},\n keywords = {MCF},\n pages = {2169},\n volume = {9},\n websites = {https://www.mdpi.com/2076-2607/9/10/2169/htm,https://www.mdpi.com/2076-2607/9/10/2169},\n month = {10},\n publisher = {MDPI},\n day = {1},\n id = {fe313604-dc45-3fa1-8e56-1ef4cbda8aaf},\n created = {2025-07-07T13:25:34.610Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:19.241Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Li, Heng and Ramia, Nancy E. and Borges, Frédéric and Revol-Junelles, Anne Marie and Vogensen, Finn Kvist and Leisner, Jørgen J.},\n doi = {10.3390/MICROORGANISMS9102169/S1},\n journal = {Microorganisms},\n number = {10}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n The ultra-structural, metabolomic and metagenomic characterisation of the sudanese smokeless tobacco 'Toombak'.\n \n \n \n \n\n\n \n Sami, A.; Elimairi, I.; Patangia, D.; Watkins, C.; Ryan, C., A.; Ross, R., P.; and Stanton, C.\n\n\n \n\n\n\n Toxicology reports, 8: 1498-1512. 1 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {The ultra-structural, metabolomic and metagenomic characterisation of the sudanese smokeless tobacco 'Toombak'},\n type = {article},\n year = {2021},\n keywords = {Semi-polar,voc},\n pages = {1498-1512},\n volume = {8},\n websites = {https://pubmed.ncbi.nlm.nih.gov/34401360/},\n month = {1},\n publisher = {Toxicol Rep},\n day = {1},\n id = {c5390701-f922-3edc-b43a-8aaf1dc38705},\n created = {2025-07-07T13:25:34.944Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:19.578Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Sami, Amel and Elimairi, Imad and Patangia, Dhrati and Watkins, Claire and Ryan, C. Anthony and Ross, R. Paul and Stanton, Catherine},\n doi = {10.1016/J.TOXREP.2021.07.008},\n journal = {Toxicology reports}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n An integrative understanding of the large metabolic shifts induced by antibiotics in critical illness.\n \n \n \n \n\n\n \n Marfil-Sánchez, A.; Zhang, L.; Alonso-Pernas, P.; Mirhakkak, M.; Mueller, M.; Seelbinder, B.; Ni, Y.; Santhanam, R.; Busch, A.; Beemelmanns, C.; Ermolaeva, M.; Bauer, M.; and Panagiotou, G.\n\n\n \n\n\n\n Gut microbes, 13(1). 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {An integrative understanding of the large metabolic shifts induced by antibiotics in critical illness},\n type = {article},\n year = {2021},\n keywords = {BA,SCFA},\n volume = {13},\n websites = {https://pubmed.ncbi.nlm.nih.gov/34793277/},\n publisher = {Gut Microbes},\n id = {b07d62d8-7bfe-34da-b4c4-9c9416f0875b},\n created = {2025-07-07T13:25:35.294Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:35.294Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1080/19490976.2021.1993598},\n journal = {Gut microbes},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Antiviral activity of bacterial TIR domains via immune signalling molecules.\n \n \n \n \n\n\n \n Ofir, G.; Herbst, E.; Baroz, M.; Cohen, D.; Millman, A.; Doron, S.; Tal, N.; Malheiro, D., B.; Malitsky, S.; Amitai, G.; and Sorek, R.\n\n\n \n\n\n\n Nature, 600(7887): 116-120. 12 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Antiviral activity of bacterial TIR domains via immune signalling molecules},\n type = {article},\n year = {2021},\n keywords = {polar},\n pages = {116-120},\n volume = {600},\n websites = {https://pubmed.ncbi.nlm.nih.gov/34853457/},\n month = {12},\n publisher = {Nature},\n day = {2},\n id = {05c4da46-ce3b-35ed-83aa-05b6203fb5a5},\n created = {2025-07-07T13:25:35.627Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:35.627Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/S41586-021-04098-7},\n journal = {Nature},\n number = {7887}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n The Kynurenine Pathway Is Upregulated by Methyl-deficient Diet and Changes Are Averted by Probiotics.\n \n \n \n \n\n\n \n Tillmann, S.; Awwad, H., M.; MacPherson, C., W.; Happ, D., F.; Treccani, G.; Geisel, J.; Tompkins, T., A.; Ueland, P., M.; Wegener, G.; and Obeid, R.\n\n\n \n\n\n\n Molecular nutrition & food research, 65(9). 5 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {The Kynurenine Pathway Is Upregulated by Methyl-deficient Diet and Changes Are Averted by Probiotics},\n type = {article},\n year = {2021},\n keywords = {MCF},\n volume = {65},\n websites = {https://pubmed.ncbi.nlm.nih.gov/33686786/},\n month = {5},\n publisher = {Mol Nutr Food Res},\n day = {1},\n id = {4fd04669-b25c-3ad8-8249-63dbbac45bcf},\n created = {2025-07-07T13:25:35.965Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:35.965Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1002/MNFR.202100078},\n journal = {Molecular nutrition & food research},\n number = {9}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Skin dysbiosis in the microbiome in atopic dermatitis is site-specific and involves bacteria, fungus and virus.\n \n \n \n \n\n\n \n Bjerre, R., D.; Holm, J., B.; Palleja, A.; Sølberg, J.; Skov, L.; and Johansen, J., D.\n\n\n \n\n\n\n BMC Microbiology, 21(1): 256. 12 2021.\n \n\n\n\n
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\n\n\n\n@article{\n title = {Skin dysbiosis in the microbiome in atopic dermatitis is site-specific and involves bacteria, fungus and virus},\n type = {article},\n year = {2021},\n keywords = {Atopic dermatitis,Skin microbiome,Dysbiosis,atopic dermatitis,bjerre,correspondence,dk,dybboe,dysbiosis,regionh,rie,skin microbiome},\n pages = {256},\n volume = {21},\n websites = {https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-021-02302-2},\n month = {12},\n publisher = {BMC Microbiology},\n day = {23},\n id = {0237aa18-c8d1-3d03-9cda-4ee537d3a270},\n created = {2025-07-07T13:25:36.301Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:20.191Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n bibtype = {article},\n author = {Bjerre, Rie Dybboe and Holm, Jacob Bak and Palleja, Albert and Sølberg, Julie and Skov, Lone and Johansen, Jeanne Duus},\n doi = {10.1186/s12866-021-02302-2},\n journal = {BMC Microbiology},\n number = {1}\n}\n\n \n\n \n \n \n \n \n \n Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism.\n \n \n \n \n\n\n \n Jensen, B., A., H.; Holm, J., B.; Larsen, I., S.; von Burg, N.; Derer, S.; Sonne, S., B.; Pærregaard, S., I.; Damgaard, M., V.; Indrelid, S., A.; Rivollier, A.; Agrinier, A.; Sulek, K.; Arnoldussen, Y., J.; Fjære, E.; Marette, A.; Angell, I., L.; Rudi, K.; Treebak, J., T.; Madsen, L.; Åkesson, C., P.; Agace, W.; Sina, C.; Kleiveland, C., R.; Kristiansen, K.; and Lea, T., E.\n\n\n \n\n\n\n Nature Communications, 12(1): 1093. 12 2021.\n \n\n\n\n
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\n\n\n@article{\n title = {Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism},\n type = {article},\n year = {2021},\n pages = {1093},\n volume = {12},\n websites = {http://www.nature.com/articles/s41467-021-21408-9},\n month = {12},\n day = {17},\n id = {dbde0b75-96d6-3abf-a606-c59f342485bc},\n created = {2025-07-07T13:25:36.735Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:20.570Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s41467-021-21408-9},\n journal = {Nature Communications},\n number = {1}\n}\n\n 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.\n
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\n \n \n\n \n \n \n \n \n \n Assessing Population Diversity of Brettanomyces Yeast Species and Identification of Strains for Brewing Applications.\n \n \n \n \n\n\n \n Colomer, M., S.; Chailyan, A.; Fennessy, R., T.; Olsson, K., F.; Johnsen, L.; Solodovnikova, N.; and Forster, J.\n\n\n \n\n\n\n Frontiers in Microbiology, 11: 495404. 4 2020.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Assessing Population Diversity of Brettanomyces Yeast Species and Identification of Strains for Brewing Applications},\n type = {article},\n year = {2020},\n keywords = {4-ethylguaiacol,Dekkera bruxellensis,beta-glucosidase,brewing fermentation,genomics,high-throughput screening,maltose assimilation,phenolic off-flavor},\n pages = {495404},\n volume = {11},\n websites = {www.frontiersin.org},\n month = {4},\n publisher = {Frontiers Media S.A.},\n day = {9},\n id = {a549cd82-02cd-329e-9797-234410706e33},\n created = {2025-07-07T13:25:25.208Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:11.389Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Colomer, Marc Serra and Chailyan, Anna and Fennessy, Ross T. and Olsson, Kim Friis and Johnsen, Lea and Solodovnikova, Natalia and Forster, Jochen},\n doi = {10.3389/FMICB.2020.00637/BIBTEX},\n journal = {Frontiers in Microbiology}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Comparative proteomic analysis of SLC13A5 knockdown reveals elevated ketogenesis and enhanced cellular toxic response to chemotherapeutic agents in HepG2 cells.\n \n \n \n \n\n\n \n Hu, T.; Huang, W.; Li, Z.; Kane, M., A.; Zhang, L.; Huang, S., M.; and Wang, H.\n\n\n \n\n\n\n Toxicology and applied pharmacology, 402. 9 2020.\n \n\n\n\n
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Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n\n
\n\n\n@article{\n title = {Comparative proteomic analysis of SLC13A5 knockdown reveals elevated ketogenesis and enhanced cellular toxic response to chemotherapeutic agents in HepG2 cells},\n type = {article},\n year = {2020},\n 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},\n volume = {402},\n websites = {https://pubmed.ncbi.nlm.nih.gov/32634519/},\n month = {9},\n publisher = {Toxicol Appl Pharmacol},\n day = {1},\n id = {13bcf20b-3b99-3076-8101-0f7006b95363},\n created = {2025-07-07T13:25:25.548Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:25.548Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Hu, Tao and Huang, Weiliang and Li, Zhihui and Kane, Maureen A. and Zhang, Lei and Huang, Shiew Mei and Wang, Hongbing},\n doi = {10.1016/J.TAAP.2020.115117},\n journal = {Toxicology and applied pharmacology}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse.\n \n \n \n \n\n\n \n Van De Wouw, M.; Walsh, A., M.; Crispie, F.; Van Leuven, L.; Lyte, J., M.; Boehme, M.; Clarke, G.; Dinan, T., G.; Cotter, P., D.; and Cryan, J., F.\n\n\n \n\n\n\n Microbiome, 8(1): 1-20. 5 2020.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse},\n type = {article},\n year = {2020},\n keywords = {MCF,SCFA},\n pages = {1-20},\n volume = {8},\n websites = {https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-020-00846-5},\n month = {5},\n publisher = {BioMed Central Ltd.},\n day = {18},\n id = {b051030c-1e77-3199-b951-131100c32425},\n created = {2025-07-07T13:25:25.913Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:11.855Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.]},\n bibtype = {article},\n 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.},\n doi = {10.1186/S40168-020-00846-5/FIGURES/9},\n journal = {Microbiome},\n number = {1}\n}\n\n 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.]\n
\n\n\n\n \n\n \n \n \n \n \n \n Encapsulated cyclosporine does not change the composition of the human microbiota when assessed ex vivo and in vivo.\n \n \n \n \n\n\n \n O'Reilly, C.; O'Sullivan, Ó.; Cotter, P., D.; O'Connor, P., M.; Shanahan, F.; Cullen, A.; Rea, M., C.; Hill, C.; Coulter, I.; and Paul Ross, R.\n\n\n \n\n\n\n Journal of Medical Microbiology, 69(6): 854. 2020.\n \n\n\n\n
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\n\n\n@article{\n title = {Encapsulated cyclosporine does not change the composition of the human microbiota when assessed ex vivo and in vivo},\n type = {article},\n year = {2020},\n keywords = {16S rRNA gene sequencing,Composition,Cyclosporine A,Functionality,Human microbiota,Short-chain fatty acids},\n pages = {854},\n volume = {69},\n websites = {/pmc/articles/PMC7451034/,/pmc/articles/PMC7451034/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451034/},\n publisher = {Microbiology Society},\n id = {09b95955-c9ee-34e3-9daa-190538a17f10},\n created = {2025-07-07T13:25:26.314Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:12.212Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1099/JMM.0.001130},\n journal = {Journal of Medical Microbiology},\n number = {6}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Gut microbiome of a porcine model of metabolic syndrome and HF-pEF.\n \n \n \n \n\n\n \n O'Donovan, A., N.; Herisson, F., M.; Fouhy, F.; Ryan, P., M.; Whelan, D.; Johnson, C., N.; Cluzel, G.; Ross, R., P.; Stanton, C.; and Caplice, N., M.\n\n\n \n\n\n\n American journal of physiology. Heart and circulatory physiology, 318(3): H590-H603. 3 2020.\n \n\n\n\n
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\n\n\n@article{\n title = {Gut microbiome of a porcine model of metabolic syndrome and HF-pEF},\n type = {article},\n year = {2020},\n 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},\n pages = {H590-H603},\n volume = {318},\n websites = {https://pubmed.ncbi.nlm.nih.gov/32031871/},\n month = {3},\n publisher = {Am J Physiol Heart Circ Physiol},\n day = {1},\n id = {4f7a4843-bff2-3acf-b2f7-a5c6bc6500ea},\n created = {2025-07-07T13:25:26.651Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:12.589Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1152/AJPHEART.00512.2019},\n journal = {American journal of physiology. Heart and circulatory physiology},\n number = {3}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Metabolomic networks and pathways associated with feed efficiency and related-traits in Duroc and Landrace pigs.\n \n \n \n \n\n\n \n Adriano Okstoft Carmelo, V.; Banerjee, P.; Jarles Da Silva Diniz, W.; and Kadarmideen, H., N.\n\n\n \n\n\n\n Scientific Report, 10(255). 2020.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Metabolomic networks and pathways associated with feed efficiency and related-traits in Duroc and Landrace pigs},\n type = {article},\n year = {2020},\n volume = {10},\n websites = {www.nature.com/scientificreports},\n id = {ec4dd6bb-30c3-35ca-80b5-f1df74a7ae2b},\n created = {2025-07-07T13:25:27.025Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:12.982Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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},\n bibtype = {article},\n author = {Adriano Okstoft Carmelo, Victor and Banerjee, Priyanka and Jarles Da Silva Diniz, Wellison and Kadarmideen, Haja N},\n doi = {10.1038/s41598-019-57182-4},\n journal = {Scientific Report},\n number = {255}\n}\n\n 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\n
\n\n\n\n \n\n \n \n \n \n \n \n Oxidant-induced modifications in the mucosal transcriptome and circulating metabolome of Atlantic salmon.\n \n \n \n \n\n\n \n Lazado, C., C.; Pedersen, L., F.; Kirste, K., H.; Soleng, M.; Breiland, M., W.; and Timmerhaus, G.\n\n\n \n\n\n\n Aquatic Toxicology, 227: 105625. 10 2020.\n \n\n\n\n
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\n\n\n@article{\n title = {Oxidant-induced modifications in the mucosal transcriptome and circulating metabolome of Atlantic salmon},\n type = {article},\n year = {2020},\n keywords = {Amoebic gill disease,Aquaculture,Disinfectant,Metabolomics,Mucosal immunity,Oxidative stress,Peroxide},\n pages = {105625},\n volume = {227},\n month = {10},\n publisher = {Elsevier},\n day = {1},\n id = {17a4b4fc-df08-34e7-82d9-8cd39e826309},\n created = {2025-07-07T13:25:27.351Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:13.241Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Lazado, Carlo C. and Pedersen, Lars Flemming and Kirste, Katrine H. and Soleng, Malene and Breiland, Mette W. and Timmerhaus, Gerrit},\n doi = {10.1016/J.AQUATOX.2020.105625},\n journal = {Aquatic Toxicology}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n 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.\n \n \n \n \n\n\n \n O'Connor, K., M.; Lucking, E., F.; Bastiaanssen, T., F.; Peterson, V., L.; Crispie, F.; Cotter, P., D.; Clarke, G.; Cryan, J., F.; and O'Halloran, K., D.\n\n\n \n\n\n\n EBioMedicine, 59. 9 2020.\n \n\n\n\n
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\n\n\n@article{\n 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},\n type = {article},\n year = {2020},\n keywords = {SCFA},\n volume = {59},\n 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},\n month = {9},\n publisher = {Elsevier B.V.},\n day = {1},\n id = {47b78574-85d5-3006-8a7a-ed92b75729d4},\n created = {2025-07-07T13:25:27.709Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:13.607Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1016/J.EBIOM.2020.102968/ATTACHMENT/9B13E164-2DF4-4796-BAE3-E3FF37C82ECF/MMC2.DOCX},\n journal = {EBioMedicine}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Staphylococcus aureus induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes.\n \n \n \n \n\n\n \n Mellergaard, M.; Høgh, R., I.; Lund, A.; Aldana, B., I.; Guérillot, R.; Møller, S., H.; Hayes, A., S.; Panagiotopoulou, N.; Frimand, Z.; Jepsen, S., D.; Hansen, C., H., F.; Andresen, L.; Larsen, A., R.; Peleg, A., Y.; Stinear, T., P.; Howden, B., P.; Waagepetersen, H., S.; Frees, D.; and Skov, S.\n\n\n \n\n\n\n Journal of Biological Chemistry, 295(33): 11803-11821. 8 2020.\n \n\n\n\n
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\n\n\n@article{\n title = {Staphylococcus aureus induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes},\n type = {article},\n year = {2020},\n 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)},\n pages = {11803-11821},\n volume = {295},\n 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},\n month = {8},\n publisher = {American Society for Biochemistry and Molecular Biology Inc.},\n day = {14},\n id = {0ef71c27-4b42-3878-b28b-f73031c7fa9c},\n created = {2025-07-07T13:25:28.066Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:13.965Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1074/JBC.RA120.012673/ATTACHMENT/E1960645-E916-45A2-8BDE-4B87A6E08B91/MMC1.PDF},\n journal = {Journal of Biological Chemistry},\n number = {33}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Chronic exposure of soybean plants to nanomolar cadmium reveals specific additional high-affinity targets of cadmium toxicity.\n \n \n \n \n\n\n \n Andresen, E.; Lyubenova, L.; Hubáček, T.; Bokhari, S., N., H.; Matoušková, Š.; Mijovilovich, A.; Rohovec, J.; and Küpper, H.\n\n\n \n\n\n\n Journal of experimental botany, 71(4): 1628-1644. 2 2020.\n \n\n\n\n
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\n\n\n@article{\n title = {Chronic exposure of soybean plants to nanomolar cadmium reveals specific additional high-affinity targets of cadmium toxicity},\n type = {article},\n year = {2020},\n 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},\n pages = {1628-1644},\n volume = {71},\n websites = {https://pubmed.ncbi.nlm.nih.gov/31760430/},\n month = {2},\n publisher = {J Exp Bot},\n day = {19},\n id = {41d05d21-6e7d-33fb-b557-0e199860f6a9},\n created = {2025-07-07T13:25:28.456Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:14.298Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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).},\n bibtype = {article},\n 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},\n doi = {10.1093/JXB/ERZ530},\n journal = {Journal of experimental botany},\n number = {4}\n}\n\n 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).\n
\n\n\n\n \n\n \n \n \n \n \n \n Prokaryotic viperins produce diverse antiviral molecules.\n \n \n \n \n\n\n \n Bernheim, A.; Millman, A.; Ofir, G.; Meitav, G.; Avraham, C.; Shomar, H.; Rosenberg, M., M.; Tal, N.; Melamed, S.; Amitai, G.; and Sorek, R.\n\n\n \n\n\n\n Nature 2020 589:7840, 589(7840): 120-124. 9 2020.\n \n\n\n\n
\n\n\n\n \n \nWebsite\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Prokaryotic viperins produce diverse antiviral molecules},\n type = {article},\n year = {2020},\n keywords = {polar},\n pages = {120-124},\n volume = {589},\n websites = {https://www.nature.com/articles/s41586-020-2762-2},\n month = {9},\n publisher = {Nature Publishing Group},\n day = {16},\n id = {7e61b953-7d4e-3981-bda5-53d64e8c5613},\n created = {2025-07-07T13:25:28.782Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:28.782Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s41586-020-2762-2},\n journal = {Nature 2020 589:7840},\n number = {7840}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse.\n \n \n \n \n\n\n \n Van De Wouw, M.; Walsh, A., M.; Crispie, F.; Van Leuven, L.; Lyte, J., M.; Boehme, M.; Clarke, G.; Dinan, T., G.; Cotter, P., D.; and Cryan, J., F.\n\n\n \n\n\n\n Microbiome, 8(1). 5 2020.\n \n\n\n\n
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\n\n\n@article{\n title = {Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse},\n type = {article},\n year = {2020},\n keywords = {Behaviour,Brain,GABA,Immunity,Kefir,Lactobacillus,Microbiota,Mouse,Reward,Serotonin},\n volume = {8},\n month = {5},\n publisher = {BioMed Central Ltd.},\n day = {18},\n id = {c5918614-0090-3110-9dff-ba57035e8870},\n created = {2025-07-07T13:25:29.125Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:14.715Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.]},\n bibtype = {article},\n 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.},\n doi = {10.1186/s40168-020-00846-5},\n journal = {Microbiome},\n number = {1}\n}\n\n 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.]\n
\n\n\n\n \n\n \n \n \n \n \n \n Interventional Influence of the Intestinal Microbiome Through Dietary Intervention and Bowel Cleansing Might Improve Motor Symptoms in Parkinson’s Disease.\n \n \n \n \n\n\n \n Hegelmaier, T.; Lebbing, M.; Duscha, A.; Tomaske, L.; Tönges, L.; Holm, J., B.; Bjørn Nielsen, H.; Gatermann, S., G.; Przuntek, H.; and Haghikia, A.\n\n\n \n\n\n\n Cells, 9(2): 376. 2 2020.\n \n\n\n\n
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\n\n\n@article{\n title = {Interventional Influence of the Intestinal Microbiome Through Dietary Intervention and Bowel Cleansing Might Improve Motor Symptoms in Parkinson’s Disease},\n type = {article},\n year = {2020},\n keywords = {butyric acid,enema,microbiome,parkinson,s disease,vegetarian diet},\n pages = {376},\n volume = {9},\n websites = {https://www.mdpi.com/2073-4409/9/2/376},\n month = {2},\n day = {6},\n id = {5925b0f6-9ade-306c-a863-0c5adca86fbd},\n created = {2025-07-07T13:25:29.457Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:15.084Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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>},\n bibtype = {article},\n 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},\n doi = {10.3390/cells9020376},\n journal = {Cells},\n number = {2}\n}\n\n
\n\n\nThe 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.
\n\n \n\n \n \n \n \n \n \n Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism.\n \n \n \n \n\n\n \n Duscha, A.; Gisevius, B.; Hirschberg, S.; Linker, R., A.; Gold, R.; and Haghikia, A.\n\n\n \n\n\n\n Cell, 180: 1-14. 2020.\n \n\n\n\n
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\n\n\n@article{\n title = {Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism},\n type = {article},\n year = {2020},\n pages = {1-14},\n volume = {180},\n websites = {https://doi.org/10.1016/j.cell.2020.02.035},\n id = {175e2b69-4b44-3ee5-aded-3e54128d6907},\n created = {2025-07-07T13:25:29.776Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:15.413Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Duscha2020},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Duscha, Alexander and Gisevius, Barbara and Hirschberg, Sarah and Linker, Ralf A and Gold, Ralf and Haghikia, Aiden},\n doi = {10.1016/j.cell.2020.02.035},\n journal = {Cell}\n}\n\n 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.\n
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\n \n \n\n \n \n \n \n \n \n Cyclic GMP–AMP signalling protects bacteria against viral infection.\n \n \n \n \n\n\n \n Cohen, D.; Melamed, S.; Millman, A.; Shulman, G.; Oppenheimer-Shaanan, Y.; Kacen, A.; Doron, S.; Amitai, G.; and Sorek, R.\n\n\n \n\n\n\n Nature 2019 574:7780, 574(7780): 691-695. 9 2019.\n \n\n\n\n
\n\n\n\n \n \nWebsite\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Cyclic GMP–AMP signalling protects bacteria against viral infection},\n type = {article},\n year = {2019},\n keywords = {polar},\n pages = {691-695},\n volume = {574},\n websites = {https://www.nature.com/articles/s41586-019-1605-5},\n month = {9},\n publisher = {Nature Publishing Group},\n day = {18},\n id = {e9a2c32d-0180-35ec-8ec0-9188777dec90},\n created = {2025-07-07T13:25:19.887Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:19.887Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s41586-019-1605-5},\n journal = {Nature 2019 574:7780},\n number = {7780}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n 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.\n \n \n \n \n\n\n \n Sales Martínez, C.\n\n\n \n\n\n\n TDX (Tesis Doctorals en Xarxa). 12 2019.\n \n\n\n\n
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\n\n\n@article{\n 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},\n type = {article},\n year = {2019},\n keywords = {543,Ciències naturals,Gas Chromatography,Mass Spectrometry,Metabolomics,Pollutants,Purge and Trap,Volatiles,físiques i matemàtiques,químiques},\n websites = {https://www.tdx.cat/handle/10803/668939},\n month = {12},\n publisher = {Universitat Jaume I},\n day = {18},\n city = {Castelló},\n institution = {Universitat Jaume I},\n department = {Química Física i Analítica},\n id = {15354d97-669a-3caf-ade5-55b843b2441b},\n created = {2025-07-07T13:25:20.219Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:06.775Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n abstract = {Programa de Doctorat en Ciències},\n bibtype = {article},\n author = {Sales Martínez, Carlos},\n doi = {10.6035/14104.2019.177055},\n journal = {TDX (Tesis Doctorals en Xarxa)}\n}\n\n Programa de Doctorat en Ciències\n
\n\n\n\n \n\n \n \n \n \n \n \n High Levels of Prebiotic Resistant Starch in Diet Modulate Gene Expression and Metabolomic Profile in Pancreatic Cancer Xenograft Mice.\n \n \n \n \n\n\n \n Panebianco, C.; Villani, A.; and Pazienza, V.\n\n\n \n\n\n\n Nutrients, 11(4). 4 2019.\n \n\n\n\n
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Paper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n\n
\n\n\n@article{\n title = {High Levels of Prebiotic Resistant Starch in Diet Modulate Gene Expression and Metabolomic Profile in Pancreatic Cancer Xenograft Mice},\n type = {article},\n year = {2019},\n 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},\n volume = {11},\n websites = {https://pubmed.ncbi.nlm.nih.gov/30934731/},\n month = {4},\n publisher = {Nutrients},\n day = {1},\n id = {86fd9c93-6684-3416-ae37-20e5ca112779},\n created = {2025-07-07T13:25:20.574Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:07.271Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Panebianco, Concetta and Villani, Annacandida and Pazienza, Valerio},\n doi = {10.3390/NU11040709},\n journal = {Nutrients},\n number = {4}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n In vitro Characterization of Gut Microbiota-Derived Bacterial Strains With Neuroprotective Properties.\n \n \n \n \n\n\n \n Ahmed, S.; Busetti, A.; Fotiadou, P.; Vincy Jose, N.; Reid, S.; Georgieva, M.; Brown, S.; Dunbar, H.; Beurket-Ascencio, G.; Delday, M., I.; Ettorre, A.; and Mulder, I., E.\n\n\n \n\n\n\n Frontiers in Cellular Neuroscience, 13: 463586. 9 2019.\n \n\n\n\n
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\n\n\n@article{\n title = {In vitro Characterization of Gut Microbiota-Derived Bacterial Strains With Neuroprotective Properties},\n type = {article},\n year = {2019},\n keywords = {gut microbiota-derived bacterial strains,gut-brain axis,microbiome,neurodegenerative diseases,neuroinflammation,neuroprotection,oxidative stress,short-chain fatty acids},\n pages = {463586},\n volume = {13},\n month = {9},\n publisher = {Frontiers Media S.A.},\n day = {20},\n id = {8ccf8162-4dd2-38c6-8611-f434b0050a53},\n created = {2025-07-07T13:25:20.920Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:07.610Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.3389/FNCEL.2019.00402/BIBTEX},\n journal = {Frontiers in Cellular Neuroscience}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR.\n \n \n \n \n\n\n \n Mogilenko, D., A.; Haas, J., T.; L'homme, L.; Fleury, S.; Quemener, S.; Levavasseur, M.; Becquart, C.; Wartelle, J.; Bogomolova, A.; Pineau, L.; Molendi-Coste, O.; Lancel, S.; Dehondt, H.; Gheeraert, C.; Melchior, A.; Dewas, C.; Nikitin, A.; Pic, S.; Rabhi, N.; Annicotte, J., S.; Oyadomari, S.; Velasco-Hernandez, T.; Cammenga, J.; Foretz, M.; Viollet, B.; Vukovic, M.; Villacreces, A.; Kranc, K.; Carmeliet, P.; Marot, G.; Boulter, A.; Tavernier, S.; Berod, L.; Longhi, M., P.; Paget, C.; Janssens, S.; Staumont-Sallé, D.; Aksoy, E.; Staels, B.; and Dombrowicz, D.\n\n\n \n\n\n\n Cell, 177(5): 1201-1216.e19. 5 2019.\n \n\n\n\n
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\n\n\n@article{\n title = {Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR},\n type = {article},\n year = {2019},\n keywords = {IL-23,UPR,dendritic cells,fatty acids,glycolysis,hexokinase,innate immunity,metabolic reprogramming,mtROS,psoriasis},\n pages = {1201-1216.e19},\n volume = {177},\n 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},\n month = {5},\n publisher = {Cell Press},\n day = {16},\n id = {43a1292a-2e1d-39dd-ad2e-1cf87a6f3bce},\n created = {2025-07-07T13:25:21.293Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:08.024Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1016/j.cell.2019.03.018},\n journal = {Cell},\n number = {5}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells.\n \n \n \n \n\n\n \n Tencerova, M.; Rendina-Ruedy, E.; Neess, D.; Færgeman, N.; Figeac, F.; Ali, D.; Danielsen, M.; Haakonsson, A.; Rosen, C., J.; and Kassem, M.\n\n\n \n\n\n\n Bone Research 2019 7:1, 7(1): 1-14. 11 2019.\n \n\n\n\n
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\n\n\n@article{\n title = {Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells},\n type = {article},\n year = {2019},\n keywords = {Bone,Fat metabolism},\n pages = {1-14},\n volume = {7},\n websites = {https://www.nature.com/articles/s41413-019-0076-5},\n month = {11},\n publisher = {Nature Publishing Group},\n day = {14},\n id = {ae03ed37-082f-3bcc-9fc0-37d3657c1bcc},\n created = {2025-07-07T13:25:21.655Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:08.339Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s41413-019-0076-5},\n journal = {Bone Research 2019 7:1},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Metabolomics Analyses in High-Low Feed Efficient Dairy Cows Reveal Novel Biochemical Mechanisms and Predictive Biomarkers.\n \n \n \n \n\n\n \n Wang, X.; and Kadarmideen, H., N.\n\n\n \n\n\n\n Metabolites, 9(7). 7 2019.\n \n\n\n\n
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\n\n\n@article{\n title = {Metabolomics Analyses in High-Low Feed Efficient Dairy Cows Reveal Novel Biochemical Mechanisms and Predictive Biomarkers},\n type = {article},\n year = {2019},\n keywords = {Dairy cattle,Gene-metabolite network,Metabolomics,Residual feed intake},\n volume = {9},\n websites = {/pmc/articles/PMC6680417/,/pmc/articles/PMC6680417/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680417/},\n month = {7},\n publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},\n day = {1},\n id = {4a577d49-ed14-3b6b-a18d-dc4ec7cf1d88},\n created = {2025-07-07T13:25:22.043Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:08.758Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Wang, Xiao and Kadarmideen, Haja N.},\n doi = {10.3390/METABO9070151},\n journal = {Metabolites},\n number = {7}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome.\n \n \n \n \n\n\n \n Boehme, M.; van de Wouw, M.; Bastiaanssen, T., F.; Olavarría-Ramírez, L.; Lyons, K.; Fouhy, F.; Golubeva, A., V.; Moloney, G., M.; Minuto, C.; Sandhu, K., V.; Scott, K., A.; Clarke, G.; Stanton, C.; Dinan, T., G.; Schellekens, H.; and Cryan, J., F.\n\n\n \n\n\n\n Molecular Psychiatry 2019 25:10, 25(10): 2567-2583. 5 2019.\n \n\n\n\n
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\n\n\n@article{\n title = {Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome},\n type = {article},\n year = {2019},\n keywords = {Molecular biology,Neuroscience},\n pages = {2567-2583},\n volume = {25},\n websites = {https://www.nature.com/articles/s41380-019-0425-1},\n month = {5},\n publisher = {Nature Publishing Group},\n day = {16},\n id = {d9fab3a7-a18a-3133-9ef8-3769fb9cfa4c},\n created = {2025-07-07T13:25:22.371Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:22.371Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1038/s41380-019-0425-1},\n journal = {Molecular Psychiatry 2019 25:10},\n number = {10}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice.\n \n \n \n \n\n\n \n Larsen, I., S.; Fritzen, A., M.; Carl, C., S.; Agerholm, M.; Damgaard, M., T., F.; Holm, J., B.; Marette, A.; Nordkild, P.; Kiens, B.; Kristiansen, K.; Wehkamp, J.; and Jensen, B., A., H.\n\n\n \n\n\n\n American Journal of Physiology - Endocrinology and Metabolism, 317(1): E42-E52. 2019.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice},\n type = {article},\n year = {2019},\n keywords = {Diet-induced obesity,Host-microbe interactions,Human defensins,Insulin resistance,NAFLD},\n pages = {E42-E52},\n volume = {317},\n id = {fd085c6f-35a2-338f-a448-990ccdcea5b2},\n created = {2025-07-07T13:25:22.708Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:09.167Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1152/ajpendo.00019.2019},\n journal = {American Journal of Physiology - Endocrinology and Metabolism},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Bifidobacterium breve Bif195 Protects Against Small-Intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers.\n \n \n \n \n\n\n \n Mortensen, B.; Murphy, C.; O'Grady, J.; Lucey, M.; Elsafi, G.; Barry, L.; Westphal, V.; Wellejus, A.; Lukjancenko, O.; Eklund, A., C.; Nielsen, H., B.; Baker, A.; Damholt, A.; van Hylckama Vlieg, J., E.; Shanahan, F.; and Buckley, M.\n\n\n \n\n\n\n Gastroenterology, 157(3): 637-646.e4. 2019.\n \n\n\n\n
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\n\n\n@article{\n title = {Bifidobacterium breve Bif195 Protects Against Small-Intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers},\n type = {article},\n year = {2019},\n keywords = {Aspirin,Bacteria,Bleeding,Microbiota},\n pages = {637-646.e4},\n volume = {157},\n websites = {https://doi.org/10.1053/j.gastro.2019.05.008},\n publisher = {The American Gastroenterological Association},\n id = {b27f9e89-5cd1-3027-95f3-43276acdde71},\n created = {2025-07-07T13:25:23.033Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:09.554Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Mortensen2019},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1053/j.gastro.2019.05.008},\n journal = {Gastroenterology},\n number = {3}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Habitat fragmentation is associated with dietary shifts and microbiota variability in common vampire bats.\n \n \n \n \n\n\n \n Ingala, M., R.; Becker, D., J.; Bak Holm, J.; Kristiansen, K.; and Simmons, N., B.\n\n\n \n\n\n\n Ecology and Evolution. 5 2019.\n \n\n\n\n
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\n\n\n@article{\n title = {Habitat fragmentation is associated with dietary shifts and microbiota variability in common vampire bats},\n type = {article},\n year = {2019},\n month = {5},\n publisher = {Wiley},\n day = {9},\n id = {dda31099-6c9f-3531-b36d-81b8fdf593f6},\n created = {2025-07-07T13:25:23.358Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:09.924Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n citation_key = {Ingala2019},\n private_publication = {false},\n 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},\n bibtype = {article},\n author = {Ingala, Melissa R. and Becker, Daniel J. and Bak Holm, Jacob and Kristiansen, Karsten and Simmons, Nancy B.},\n doi = {10.1002/ece3.5228},\n journal = {Ecology and Evolution}\n}\n\n 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\n
\n\n\n\n \n\n \n \n \n \n \n Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism.\n \n \n \n\n\n \n 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, T., E., L.\n\n\n \n\n\n\n bioRxiv. 2019.\n \n\n\n\n
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\n\n\n@article{\n title = {Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism},\n type = {article},\n year = {2019},\n id = {fa409164-55a2-37a7-aebb-5f7e7c021752},\n created = {2025-07-07T13:25:23.716Z},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:23.716Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Benjamin.A.H.JensenJacobB.HolmIdaS.LarsenNicolevonBurgStefanieDererAymericRivollierAnneLaureAgrinierKarolinaSulekStineA.IndrelidYkeJ.ArnoldussenSiB.SonneEvenFjæreMadsT.F.DamgaardSimoneI.PærregaardInga2019},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {https://doi.org/10.1101/855486},\n journal = {bioRxiv}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer.\n \n \n \n \n\n\n \n Wirbel, J.; Pyl, P., T.; Kartal, E.; Zych, K.; Kashani, A.; Milanese, A.; Fleck, J., S.; Voigt, A., Y.; Palleja, A.; Ponnudurai, R.; Sunagawa, S.; Coelho, L., P.; Schrotz-King, P.; Vogtmann, E.; Habermann, N.; Niméus, E.; Thomas, A., M.; Manghi, P.; Gandini, S.; Serrano, D.; Mizutani, S.; Shiroma, H.; Shiba, S.; Shibata, T.; Yachida, S.; Yamada, T.; Waldron, L.; Naccarati, A.; Segata, N.; Sinha, R.; Ulrich, C., M.; Brenner, H.; Arumugam, M.; Bork, P.; and Zeller, G.\n\n\n \n\n\n\n Nature Medicine, 25(4): 679-689. 2019.\n \n\n\n\n
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\n\n\n@article{\n title = {Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer},\n type = {article},\n year = {2019},\n pages = {679-689},\n volume = {25},\n websites = {http://dx.doi.org/10.1038/s41591-019-0406-6},\n publisher = {Springer US},\n id = {317090a9-cede-38c1-8c2c-56cec07b99b9},\n created = {2025-07-07T13:25:24.181Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:10.341Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Wirbel2019},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s41591-019-0406-6},\n journal = {Nature Medicine},\n number = {4}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice.\n \n \n \n \n\n\n \n Madsen, M., S., A.; Holm, J., B.; Pallejà, A.; Wismann, P.; Fabricius, K.; Rigbolt, K.; Mikkelsen, M.; Sommer, M.; Jelsing, J.; Nielsen, H., B.; Vrang, N.; and Hansen, H., H.\n\n\n \n\n\n\n Scientific Reports, 9(1): 15582. 2019.\n \n\n\n\n
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\n\n\n\n@article{\n title = {Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice},\n type = {article},\n year = {2019},\n pages = {15582},\n volume = {9},\n websites = {http://www.nature.com/articles/s41598-019-52103-x},\n id = {a5d31967-b49a-3bcd-bedb-73f15f5ec20b},\n created = {2025-07-07T13:25:24.519Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:10.708Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Madsen2019},\n private_publication = {false},\n bibtype = {article},\n 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.},\n doi = {10.1038/s41598-019-52103-x},\n journal = {Scientific Reports},\n number = {1}\n}\n\n \n\n \n \n \n \n \n \n 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.\n \n \n \n \n\n\n \n Munch Roager, H.; Vogt, J., K.; Kristensen, M.; Hansen, L., B., S.; Ibrügger, S.; Maerkedahl, R., B.; Bahl, M., I.; Lind, M., V.; Nielsen, R., L.; Frøkiaer, H.; Gøbel, R., J.; Landberg, R.; Ross, A., B.; Brix, S.; Holck, J.; Meyer, A., S.; Sparholt, M., H.; Christensen, A., F.; Carvalho, V.; Hartmann, B.; Holst, J., J.; Rumessen, J., J.; Linneberg, A.; Sicheritz-Pontén, T.; Dalgaard, M., D.; Blennow, A.; Frandsen, H., L.; Villas-Bôas, S.; Kristiansen, K.; Vestergaard, H.; Hansen, T.; Ekstrøm, C., T.; Ritz, C.; Nielsen, H., B.; Pedersen, O., B.; Gupta, R.; Lauritzen, L.; and Licht, T., R.\n\n\n \n\n\n\n Gut, 68(1): 83-93. 2019.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
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\n\n\n@article{\n 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},\n type = {article},\n year = {2019},\n pages = {83-93},\n volume = {68},\n id = {6788709d-bafb-3b86-9014-5f0f57769292},\n created = {2025-07-07T13:25:24.866Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:11.042Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {MunchRoager2019},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1136/gutjnl-2017-314786},\n journal = {Gut},\n number = {1}\n}\n\n 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.\n
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\n \n \n\n \n \n \n \n \n \n Antibiotic treatment of rat dams affects bacterial colonization and causes decreased weight gain in pups.\n \n \n \n \n\n\n \n Tulstrup, M., V., L.; Roager, H., M.; Thaarup, I., C.; Frandsen, H., L.; Frøkiær, H.; Licht, T., R.; and Bahl, M., I.\n\n\n \n\n\n\n Communications biology, 1(1). 12 2018.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Antibiotic treatment of rat dams affects bacterial colonization and causes decreased weight gain in pups},\n type = {article},\n year = {2018},\n 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},\n volume = {1},\n websites = {https://pubmed.ncbi.nlm.nih.gov/30272021/},\n month = {12},\n publisher = {Commun Biol},\n day = {1},\n id = {c3d43ee6-af53-3a5a-813a-b1349a99f8fa},\n created = {2025-07-07T13:25:15.876Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:03.133Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/S42003-018-0140-5},\n journal = {Communications biology},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation.\n \n \n \n \n\n\n \n Brandt, C.; Nolte, H.; Henschke, S.; Engström Ruud, L.; Awazawa, M.; Morgan, D., A.; Gabel, P.; Sprenger, H., G.; Hess, M., E.; Günther, S.; Langer, T.; Rahmouni, K.; Fenselau, H.; Krüger, M.; and Brüning, J., C.\n\n\n \n\n\n\n Cell, 175(5): 1321-1335.e20. 11 2018.\n \n\n\n\n
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\n\n\n@article{\n title = {Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation},\n type = {article},\n year = {2018},\n pages = {1321-1335.e20},\n volume = {175},\n 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},\n month = {11},\n publisher = {Cell Press},\n day = {15},\n id = {f59eb44c-2474-3aed-9944-72139f25069e},\n created = {2025-07-07T13:25:16.259Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:03.463Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1016/J.CELL.2018.10.015/ATTACHMENT/248FD5C3-E306-4966-AB5E-D7E6DB91C76B/MMC5.XLSX},\n journal = {Cell},\n number = {5}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Glyphosate has limited short-term effects on commensal bacterial community composition in the gut environment due to sufficient aromatic amino acid levels.\n \n \n \n \n\n\n \n Nielsen, L., N.; Roager, H., M.; Casas, M., E.; Frandsen, H., L.; Gosewinkel, U.; Bester, K.; Licht, T., R.; Hendriksen, N., B.; and Bahl, M., I.\n\n\n \n\n\n\n Environmental Pollution, 233: 364-376. 2 2018.\n \n\n\n\n
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\n\n\n@article{\n title = {Glyphosate has limited short-term effects on commensal bacterial community composition in the gut environment due to sufficient aromatic amino acid levels},\n type = {article},\n year = {2018},\n keywords = {Aromatic amino acid,Glyfonova®,Glyphosate,Gut,Intestinal,MIC,Microbiota,Roundup®},\n pages = {364-376},\n volume = {233},\n month = {2},\n publisher = {Elsevier},\n day = {1},\n id = {4b7dbb1a-24df-3a57-87bc-6e7b483bac05},\n created = {2025-07-07T13:25:16.598Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:03.797Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1016/J.ENVPOL.2017.10.016},\n journal = {Environmental Pollution}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Human gut bacteria as potent class I histone deacetylase inhibitors in vitro through production of butyric acid and valeric acid.\n \n \n \n \n\n\n \n Yuille, S.; Reichardt, N.; Panda, S.; Dunbar, H.; and Mulder, I., E.\n\n\n \n\n\n\n PLOS ONE, 13(7): e0201073. 7 2018.\n \n\n\n\n
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\n\n\n@article{\n title = {Human gut bacteria as potent class I histone deacetylase inhibitors in vitro through production of butyric acid and valeric acid},\n type = {article},\n year = {2018},\n keywords = {Butyric acids,Colorectal cancer,Consortia,Epigenetics,Gut bacteria,Histones,Metabolites,Protein extraction},\n pages = {e0201073},\n volume = {13},\n websites = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201073},\n month = {7},\n publisher = {Public Library of Science},\n day = {1},\n id = {20318f3c-2fc0-31d2-9d80-19f13855da53},\n created = {2025-07-07T13:25:17.073Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:04.149Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Yuille, Samantha and Reichardt, Nicole and Panda, Suchita and Dunbar, Hayley and Mulder, Imke E.},\n doi = {10.1371/JOURNAL.PONE.0201073},\n journal = {PLOS ONE},\n number = {7}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Influence of gemcitabine chemotherapy on the microbiota of pancreatic cancer xenografted mice.\n \n \n \n \n\n\n \n Panebianco, C.; Adamberg, K.; Jaagura, M.; Copetti, M.; Fontana, A.; Adamberg, S.; Kolk, K.; Vilu, R.; Andriulli, A.; and Pazienza, V.\n\n\n \n\n\n\n Cancer Chemotherapy and Pharmacology, 81(4): 773-782. 4 2018.\n \n\n\n\n
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\n\n\n@article{\n title = {Influence of gemcitabine chemotherapy on the microbiota of pancreatic cancer xenografted mice},\n type = {article},\n year = {2018},\n keywords = {Gemcitabine,Inflammation,Microbiota,Pancreatic cancer},\n pages = {773-782},\n volume = {81},\n websites = {https://link.springer.com/article/10.1007/s00280-018-3549-0},\n month = {4},\n publisher = {Springer Verlag},\n day = {1},\n id = {6b925428-a01c-30fa-9ad3-478e2e0ed463},\n created = {2025-07-07T13:25:17.426Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:17.426Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1007/S00280-018-3549-0/METRICS},\n journal = {Cancer Chemotherapy and Pharmacology},\n number = {4}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Streptococcus pneumoniae - stress hormone interactions.\n \n \n \n \n\n\n \n Fayez Abdullah Alghofaili, b.; and Abdullah Alghofaili, F.\n\n\n \n\n\n\n Ph.D. Thesis, 2 2018.\n \n\n\n\n
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\n\n\n@phdthesis{\n title = {Streptococcus pneumoniae - stress hormone interactions},\n type = {phdthesis},\n year = {2018},\n keywords = {IR content},\n websites = {/articles/thesis/Streptococcus_pneumoniae_-_stress_hormone_interactions/10216121/1},\n month = {2},\n publisher = {University of Leicester},\n day = {26},\n id = {9ecc4cf4-9a3b-37f5-9aeb-0979add99edf},\n created = {2025-07-07T13:25:17.744Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:04.574Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {phdthesis},\n author = {Fayez Abdullah Alghofaili, by and Abdullah Alghofaili, Fayez}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n A computational framework to integrate high-throughput ‘-omics’ datasets for the identification of potential mechanistic links.\n \n \n \n \n\n\n \n Pedersen, H., K.; Forslund, S., K.; Gudmundsdottir, V.; Petersen, A., Ø.; Hildebrand, F.; Hyötyläinen, T.; Nielsen, T.; Hansen, T.; Bork, P.; Ehrlich, S., D.; Brunak, S.; Oresic, M.; Pedersen, O.; and Nielsen, H., B.\n\n\n \n\n\n\n Nature Protocols, 13(12): 2781-2800. 2018.\n \n\n\n\n
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\n\n\n@article{\n title = {A computational framework to integrate high-throughput ‘-omics’ datasets for the identification of potential mechanistic links},\n type = {article},\n year = {2018},\n pages = {2781-2800},\n volume = {13},\n id = {ad38f124-ffb8-3745-96aa-d4bf99743c4a},\n created = {2025-07-07T13:25:18.061Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:04.930Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Pedersen2018},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s41596-018-0064-z},\n journal = {Nature Protocols},\n number = {12}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults.\n \n \n \n \n\n\n \n Hansen, L., B.; Roager, H., M.; Søndertoft, N., B.; Gøbel, R., J.; Kristensen, M.; Vallès-Colomer, M.; Vieira-Silva, S.; Ibrügger, S.; Lind, M., V.; Mærkedahl, R., B.; Bahl, M., I.; Madsen, M., L.; Havelund, J.; Falony, G.; Tetens, I.; Nielsen, T.; Allin, K., H.; Frandsen, H., L.; Hartmann, B.; Holst, J., J.; Sparholt, M., H.; Holck, J.; Blennow, A.; Moll, J., M.; Meyer, A., S.; Hoppe, C.; Poulsen, J., H.; Carvalho, V.; Sagnelli, D.; Dalgaard, M., D.; Christensen, A., F.; Lydolph, M., C.; Ross, A., B.; Villas-Bôas, S.; Brix, S.; Sicheritz-Pontén, T.; Buschard, K.; Linneberg, A.; Rumessen, J., J.; Ekstrøm, C., T.; Ritz, C.; Kristiansen, K.; Nielsen, H., B.; Vestergaard, H.; Færgeman, N., J.; Raes, J.; Frøkiær, H.; Hansen, T.; Lauritzen, L.; Gupta, R.; Licht, T., R.; and Pedersen, O.\n\n\n \n\n\n\n Nature Communications, 9(1). 2018.\n \n\n\n\n
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\n\n\n@article{\n title = {A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults},\n type = {article},\n year = {2018},\n volume = {9},\n id = {b1dcf237-e3d3-3597-8510-823ea724f3ba},\n created = {2025-07-07T13:25:18.559Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:05.269Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Hansen2018},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/s41467-018-07019-x},\n journal = {Nature Communications},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Mechanisms Preserving Insulin Action during High Dietary Fat Intake.\n \n \n \n \n\n\n \n Lundsgaard, A.; Holm, J., B.; Sjøberg, K., A.; Bojsen-Møller, K., N.; Myrmel, L., S.; Fjære, E.; Jensen, B., A.; Nicolaisen, T., S.; Hingst, J., R.; Hansen, S., L.; Doll, S.; Geyer, P., E.; Desmukh, A., S.; Holst, J., J.; Madsen, L.; Kristiansen, K.; Wojtaszewski, J., F.; Richter, E., A.; and Kiens, B.\n\n\n \n\n\n\n Cell Metabolism,1-14. 2018.\n \n\n\n\n
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\n\n\n\n@article{\n title = {Mechanisms Preserving Insulin Action during High Dietary Fat Intake},\n type = {article},\n year = {2018},\n pages = {1-14},\n websites = {https://linkinghub.elsevier.com/retrieve/pii/S1550413118305655},\n publisher = {Elsevier Inc.},\n id = {2d3a8cd2-bc3d-3b57-9e3d-0f2cf76dbef5},\n created = {2025-07-07T13:25:18.896Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:05.615Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Lundsgaard2018},\n private_publication = {false},\n bibtype = {article},\n 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},\n doi = {10.1016/j.cmet.2018.08.022},\n journal = {Cell Metabolism}\n}\n\n \n\n \n \n \n \n \n \n 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.\n \n \n \n \n\n\n \n Hjorth, M., F.; Blædel, T.; Bendtsen, L., Q.; Lorenzen, J., K.; Holm, J., B.; Kiilerich, P.; Roager, H., M.; Kristiansen, K.; Larsen, L., H.; and Astrup, A.\n\n\n \n\n\n\n International Journal of Obesity. 2018.\n \n\n\n\n
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\n\n\n\n@article{\n 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.},\n type = {article},\n year = {2018},\n websites = {http://dx.doi.org/10.1038/s41366-018-0093-2},\n publisher = {Springer US},\n id = {ee8eb6fc-28df-398c-ad8f-b66855849eeb},\n created = {2025-07-07T13:25:19.227Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:05.959Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Hjorth2018},\n private_publication = {false},\n bibtype = {article},\n 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},\n doi = {(In press)},\n journal = {International Journal of Obesity}\n}\n\n \n\n \n \n \n \n \n \n Recovery of gut microbiota of healthy adults following antibiotic exposure.\n \n \n \n \n\n\n \n Palleja, A.; Mikkelsen, K., H.; Forslund, S., K.; Kashani, A.; Allin, K., H.; Nielsen, T.; Hansen, T., H.; Liang, S.; Feng, Q.; Zhang, C.; Pyl, P., T.; Coelho, L., P.; Yang, H.; Wang, J.; Typas, A.; Nielsen, M., F.; Nielsen, H., B.; Bork, P.; Wang, J.; Vilsbøll, T.; Hansen, T.; Knop, F., K.; Arumugam, M.; and Pedersen, O.\n\n\n \n\n\n\n Nature Microbiology, 3(11): 1255-1265. 11 2018.\n \n\n\n\n
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\n\n\n\n@article{\n title = {Recovery of gut microbiota of healthy adults following antibiotic exposure},\n type = {article},\n year = {2018},\n pages = {1255-1265},\n volume = {3},\n websites = {http://www.nature.com/articles/s41564-018-0257-9},\n month = {11},\n day = {22},\n id = {36dd3c7c-7cf6-362d-8069-f7a059f1a586},\n created = {2025-07-07T13:25:19.562Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:06.298Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Palleja2018},\n private_publication = {false},\n bibtype = {article},\n 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},\n doi = {10.1038/s41564-018-0257-9},\n journal = {Nature Microbiology},\n number = {11}\n}\n\n
\n\n \n \n 2017\n \n \n (7)\n \n \n
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\n \n \n\n \n \n \n \n \n \n A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis.\n \n \n \n \n\n\n \n Fouhy, F.; Ronan, N., J.; O'Sullivan, O.; McCarthy, Y.; Walsh, A., M.; Murphy, D., M.; Daly, M.; Flanagan, E., T.; Fleming, C.; McCarthy, M.; Shortt, C.; Eustace, J., A.; Shanahan, F.; Rea, M., C.; Ross, R., P.; Stanton, C.; and Plant, B., J.\n\n\n \n\n\n\n Scientific Reports 2017 7:1, 7(1): 1-12. 7 2017.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis},\n type = {article},\n year = {2017},\n keywords = {Bacterial genes,Dysbiosis,Metagenomics},\n pages = {1-12},\n volume = {7},\n websites = {https://www.nature.com/articles/s41598-017-06880-y},\n month = {7},\n publisher = {Nature Publishing Group},\n day = {27},\n id = {7dc59654-aeaf-3868-b402-21942434f060},\n created = {2025-07-07T13:25:13.387Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:00.616Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1038/s41598-017-06880-y},\n journal = {Scientific Reports 2017 7:1},\n number = {1}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Conversion of glycerol to 3-hydroxypropanoic acid by genetically engineered Bacillus subtilis.\n \n \n \n \n\n\n \n Kalantari, A.; Chen, T.; Ji, B.; Stancik, I., A.; Ravikumar, V.; Franjevic, D.; Saulou-Bérion, C.; Goelzer, A.; and Mijakovic, I.\n\n\n \n\n\n\n Frontiers in Microbiology, 8(APR): 254491. 4 2017.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Conversion of glycerol to 3-hydroxypropanoic acid by genetically engineered Bacillus subtilis},\n type = {article},\n year = {2017},\n keywords = {3-hydroxypropanoic acid,Bacillus subtilis,Glycerol,Glycerol kinase knock-out,Metabolic engineering},\n pages = {254491},\n volume = {8},\n websites = {www.frontiersin.org},\n month = {4},\n publisher = {Frontiers Research Foundation},\n day = {18},\n id = {c560c7a4-d3f7-30df-b8b8-57505ba237a0},\n created = {2025-07-07T13:25:13.745Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:01.012Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.3389/FMICB.2017.00638/BIBTEX},\n journal = {Frontiers in Microbiology},\n number = {APR}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Deficiency of essential dietary n-3 PUFA disrupts the caecal microbiome and metabolome in mice.\n \n \n \n \n\n\n \n Robertson, R., C.; Seira Oriach, C.; Murphy, K.; Moloney, G., M.; Cryan, J., F.; Dinan, T., G.; Ross, R., P.; and Stanton, C.\n\n\n \n\n\n\n British Journal of Nutrition, 118(11): 959-970. 12 2017.\n \n\n\n\n
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\n\n\n@article{\n title = {Deficiency of essential dietary n-3 PUFA disrupts the caecal microbiome and metabolome in mice},\n type = {article},\n year = {2017},\n keywords = {Metabolomics,Microbiome,Microbiota,SCFA,control,fatty acid methyl esters,n-3 PUFA,n-3 deficient,n-3 supplemented,tricarboxylic acid},\n pages = {959-970},\n volume = {118},\n 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},\n month = {12},\n publisher = {Cambridge University Press},\n day = {14},\n id = {83d93928-2fc2-382b-a7c1-46ed8025c7c9},\n created = {2025-07-07T13:25:14.173Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:01.369Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1017/S0007114517002999},\n journal = {British Journal of Nutrition},\n number = {11}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Gas chromatography – mass spectrometry data processing made easy.\n \n \n \n \n\n\n \n Johnsen, L., G.; Skou, P., B.; Khakimov, B.; and Bro, R.\n\n\n \n\n\n\n Journal of Chromatography A, 1503: 57-64. 6 2017.\n \n\n\n\n
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\n\n\n@article{\n title = {Gas chromatography – mass spectrometry data processing made easy},\n type = {article},\n year = {2017},\n keywords = {Chromatography,Data processing,Deconvolution,GC–MS,PARAFAC2},\n pages = {57-64},\n volume = {1503},\n month = {6},\n publisher = {Elsevier},\n day = {23},\n id = {77be4b3a-0bd0-3123-b2c9-a2a2d3a7e8c6},\n created = {2025-07-07T13:25:14.495Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:01.697Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Johnsen, Lea G. and Skou, Peter B. and Khakimov, Bekzod and Bro, Rasmus},\n doi = {10.1016/J.CHROMA.2017.04.052},\n journal = {Journal of Chromatography A}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n 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.\n \n \n \n \n\n\n \n Bendtsen, L., Q.; Blædel, T.; Holm, J., B.; Lorenzen, J., K.; Mark, A., B.; Kiilerich, P.; Kristiansen, K.; Astrup, A.; and Larsen, L., H.\n\n\n \n\n\n\n Applied Physiology, Nutrition, and Metabolism, 10(August): apnm-2017-0234. 2017.\n \n\n\n\n
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\n\n\n@article{\n 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},\n type = {article},\n year = {2017},\n 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},\n pages = {apnm-2017-0234},\n volume = {10},\n websites = {http://www.nrcresearchpress.com/doi/10.1139/apnm-2017-0234},\n id = {93417085-e62b-3ff2-8a7f-d499e3c26660},\n created = {2025-07-07T13:25:14.820Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:02.027Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1139/apnm-2017-0234},\n journal = {Applied Physiology, Nutrition, and Metabolism},\n number = {August}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour.\n \n \n \n \n\n\n \n Hay-Schmidt, A.; Finkielman, O., T., E.; Jensen, B., A., H.; Høgsbro, C., F.; Bak Holm, J.; Johansen, K., H.; Jensen, T., K.; Andrade, A., M.; Swan, S., H.; Bornehag, C.; Brunak, S.; Jegou, B.; Kristiansen, K.; and Kristensen, D., M.\n\n\n \n\n\n\n Reproduction (Cambridge, England), 154(2): 145-152. 8 2017.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
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\n\n\n@article{\n title = {Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour.},\n type = {article},\n year = {2017},\n pages = {145-152},\n volume = {154},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/28559473},\n month = {8},\n id = {ac2134b5-5b00-33f3-a6e0-2942cde8b9cb},\n created = {2025-07-07T13:25:15.200Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:02.371Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1530/REP-17-0165},\n journal = {Reproduction (Cambridge, England)},\n number = {2}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat.\n \n \n \n \n\n\n \n Damgaard, M., T., F.; Pærregaard, S., I.; Søgaard, I.; Agerholm, M.; Paulson, J., N.; Treebak, J., T.; Sina, C.; Holm, J., B.; Kristiansen, K.; and Jensen, B., A., H.\n\n\n \n\n\n\n The Journal of Nutritional Biochemistry, 54: 66-76. 2017.\n \n\n\n\n
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\n\n\n\n@article{\n title = {Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat},\n type = {article},\n year = {2017},\n 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},\n pages = {66-76},\n volume = {54},\n websites = {http://dx.doi.org/10.1016/j.jnutbio.2017.09.026},\n publisher = {Elsevier Inc.},\n id = {062bfcc0-a75c-3e56-b2f8-de3a128b11d4},\n created = {2025-07-07T13:25:15.539Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:02.784Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n bibtype = {article},\n 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},\n doi = {10.1016/j.jnutbio.2017.09.026},\n journal = {The Journal of Nutritional Biochemistry}\n}\n\n
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\n \n \n\n \n \n \n \n \n \n Glucose metabolism via the entner-doudoroff pathway in campylobacter: A rare trait that enhances survival and promotes biofilm formation in some isolates.\n \n \n \n \n\n\n \n Vegge, C., S.; Jansen van Rensburg, M., J.; Rasmussen, J., J.; Maiden, M., C.; Johnsen, L., G.; Danielsen, M.; MacIntyre, S.; Ingmer, H.; and Kelly, D., J.\n\n\n \n\n\n\n Frontiers in Microbiology, 7(NOV). 11 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {Glucose metabolism via the entner-doudoroff pathway in campylobacter: A rare trait that enhances survival and promotes biofilm formation in some isolates},\n type = {article},\n year = {2016},\n keywords = {Capsule,Glycolysis,Hexose sugar,Polysaccharide,PubMLST database,Stationary-phase},\n volume = {7},\n websites = {/pmc/articles/PMC5118423/,/pmc/articles/PMC5118423/?report=abstract,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118423/},\n month = {11},\n publisher = {Frontiers Media S.A.},\n day = {22},\n id = {d457c811-abdb-3d78-8b5a-1284c1c36321},\n created = {2025-07-07T13:25:08.154Z},\n accessed = {2024-04-11},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:55.950Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.3389/FMICB.2016.01877/FULL},\n journal = {Frontiers in Microbiology},\n number = {NOV}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Removal of Polysorbate 80 by complexation prior to LC-MS analysis.\n \n \n \n \n\n\n \n Jäpelt, K., B.; Johnsen, L., G.; and Christensen, J., H.\n\n\n \n\n\n\n Analytical and Bioanalytical Chemistry, 408(9): 2303-2307. 3 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {Removal of Polysorbate 80 by complexation prior to LC-MS analysis},\n type = {article},\n year = {2016},\n keywords = {Detergent,Liquid chromatography,Mass spectrometry,Metabolite analysis,Tween 80},\n pages = {2303-2307},\n volume = {408},\n websites = {https://link.springer.com/article/10.1007/s00216-016-9326-1},\n month = {3},\n publisher = {Springer Verlag},\n day = {1},\n id = {6ff6d04e-7dc6-3813-9f51-a17bba1d2e20},\n created = {2025-07-07T13:25:08.501Z},\n accessed = {2024-04-11},\n file_attached = {false},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:08.501Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Jäpelt, Kristina B. and Johnsen, Lea Giørtz and Christensen, Jan H.},\n doi = {10.1007/S00216-016-9326-1/METRICS},\n journal = {Analytical and Bioanalytical Chemistry},\n number = {9}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n A randomised, controlled, crossover study of the effect of diet on angiopoietin-like protein 4 (ANGPTL4) through modification of the gut microbiome.\n \n \n \n \n\n\n \n Blaedel, T.; Holm, J., B.; Sundekilde, U., K.; Schmedes, M., S.; Hess, A., L.; Lorenzen, J., K.; Kristiansen, K.; Dalsgaard, T., K.; Astrup, A.; and Larsen, L., H.\n\n\n \n\n\n\n Journal of Nutritional Science, 5(10). 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {A randomised, controlled, crossover study of the effect of diet on angiopoietin-like protein 4 (ANGPTL4) through modification of the gut microbiome},\n type = {article},\n year = {2016},\n keywords = {Angiopoietin-like protein 4,Gut microbiome,Lipid metabolism,Lipoprotein lipase,Obesity},\n volume = {5},\n id = {a05b09c0-d919-314a-9fa9-c63af9084014},\n created = {2025-07-07T13:25:08.854Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:56.382Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1017/jns.2016.38},\n journal = {Journal of Nutritional Science},\n number = {10}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Intrauterine exposure to paracetamol and aniline impairs female reproductive development by reducing follicle reserves and fertility.\n \n \n \n \n\n\n \n Holm, J., B.; Mazaud-Guittot, S.; Danneskiold-Samsøe, N., B.; Chalmey, C.; Jensen, B.; Nørregård, M., M.; Hansen, C., H.; Styrishave, B.; Svingen, T.; Vinggaard, A., M.; Koch, H., M.; Bowles, J.; Koopman, P.; Jégou, B.; Kristiansen, K.; and Kristensen, D., M.\n\n\n \n\n\n\n Toxicological sciences : an official journal of the Society of Toxicology, 0(0): kfv332-. 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {Intrauterine exposure to paracetamol and aniline impairs female reproductive development by reducing follicle reserves and fertility.},\n type = {article},\n year = {2016},\n 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-},\n pages = {kfv332-},\n volume = {0},\n websites = {http://toxsci.oxfordjournals.org/content/early/2016/01/04/toxsci.kfv332.abstract},\n id = {c0cf4649-2565-33e7-8d2b-987e9d210e11},\n created = {2025-07-07T13:25:09.217Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:56.749Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Holm2016a},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1093/toxsci/kfv332},\n journal = {Toxicological sciences : an official journal of the Society of Toxicology},\n number = {0}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain.\n \n \n \n \n\n\n \n Jensen, B., A.; Nielsen, T., S.; Fritzen, A., M.; Holm, J., B.; Fjære, E.; Serup, A., K.; Borkowski, K.; Risis, S.; Pærregaard, S., I.; Søgaard, I.; Poupeau, A.; Poulsen, M.; Ma, T.; Sina, C.; Kiens, B.; Madsen, L.; Kristiansen, K.; and Treebak, J., T.\n\n\n \n\n\n\n Metabolism. 2016.\n \n\n\n\n
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\n\n\n\n@article{\n title = {Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain},\n type = {article},\n year = {2016},\n websites = {http://dx.doi.org/10.1016/j.metabol.2016.09.002,http://linkinghub.elsevier.com/retrieve/pii/S0026049516301081},\n publisher = {Elsevier B.V.},\n id = {ae986e7c-49f2-3f6a-a0ff-c56cfe3764c1},\n created = {2025-07-07T13:25:09.576Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:57.126Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n bibtype = {article},\n 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.},\n doi = {10.1016/j.metabol.2016.09.002},\n journal = {Metabolism}\n}\n\n \n\n \n \n \n \n \n \n IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis.\n \n \n \n \n\n\n \n Luda, K., M.; Joeris, T.; Persson, E., K.; Rivollier, A.; Demiri, M.; Sitnik, K., M.; Pool, L.; Holm, J., B.; Melo-Gonzalez, F.; Richter, L.; Lambrecht, B., N.; Kristiansen, K.; Travis, M., A.; Svensson-Frej, M.; Kotarsky, K.; and Agace, W., W.\n\n\n \n\n\n\n Immunity, 44(4): 860-874. 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis},\n type = {article},\n year = {2016},\n pages = {860-874},\n volume = {44},\n websites = {http://dx.doi.org/10.1016/j.immuni.2016.02.008},\n publisher = {Elsevier Inc.},\n id = {38ecedbc-0ec4-34e3-97c7-f6014e2bbc23},\n created = {2025-07-07T13:25:09.938Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:57.453Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Luda2016},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1016/j.immuni.2016.02.008},\n journal = {Immunity},\n number = {4}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Acute infection with the intestinal parasite Trichuris muris has long-term consequences on mucosal mast cell homeostasis and epithelial integrity.\n \n \n \n \n\n\n \n Sorobetea, D.; Holm, J., B.; Henningsson, H.; Kristiansen, K.; and Svensson-Frej, M.\n\n\n \n\n\n\n European journal of immunology,1-12. 11 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {Acute infection with the intestinal parasite Trichuris muris has long-term consequences on mucosal mast cell homeostasis and epithelial integrity.},\n type = {article},\n year = {2016},\n keywords = {Acute parasite infection,Large-intestinal epithelium,MCPt-1,Mucosal mast cell,Trichuris muris},\n pages = {1-12},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/27891580},\n month = {11},\n day = {28},\n id = {5b1e3a63-6cde-3288-a430-e54e6c666142},\n created = {2025-07-07T13:25:10.300Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:57.781Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Sorobetea, Daniel and Holm, Jacob Bak and Henningsson, Henrietta and Kristiansen, Karsten and Svensson-Frej, Marcus},\n doi = {10.1002/eji.201646738},\n journal = {European journal of immunology}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n The protein source determines the potential of high protein diets to attenuate obesity development in C57BL/6J mice.\n \n \n \n \n\n\n \n Liisberg, U.; Myrmel, L., S.; Fjære, E.; Rønnevik, A., K.; Bjelland, S.; Fauske, K., R.; Holm, J., B.; Basse, A., L.; Hansen, J., B.; Liaset, B.; Kristiansen, K.; and Madsen, L.\n\n\n \n\n\n\n Adipocyte, 5(2): 196-211. 2016.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {The protein source determines the potential of high protein diets to attenuate obesity development in C57BL/6J mice.},\n type = {article},\n year = {2016},\n keywords = {adiposity,animal models,brown adipose tissue,diet,protein sources},\n pages = {196-211},\n volume = {5},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/27386160,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4916867},\n id = {dd6a1284-db2a-3478-846e-cbc84653ca26},\n created = {2025-07-07T13:25:10.663Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:58.161Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Liisberg2016},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1080/21623945.2015.1122855},\n journal = {Adipocyte},\n number = {2}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Capturing one of the human gut microbiome's most wanted: Reconstructing the genome of a novel butyrate-producing, clostridial scavenger from metagenomic sequence data.\n \n \n \n \n\n\n \n Jeraldo, P.; Hernandez, A.; Nielsen, H., B.; Chen, X.; White, B., A.; Goldenfeld, N.; Nelson, H.; Alhquist, D.; Boardman, L.; and Chia, N.\n\n\n \n\n\n\n Frontiers in Microbiology, 7(MAY): 1-13. 2016.\n \n\n\n\n
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\n\n\n@article{\n 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},\n type = {article},\n year = {2016},\n keywords = {Binning,Butyricicoccus,Genome assembly,Metagenomics,Microbiome},\n pages = {1-13},\n volume = {7},\n id = {01f62de9-eb21-340f-9188-c9cb6e74b370},\n created = {2025-07-07T13:25:11.075Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:58.527Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Jeraldo2016},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.3389/fmicb.2016.00783},\n journal = {Frontiers in Microbiology},\n number = {MAY}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut.\n \n \n \n \n\n\n \n Roager, H., M.; Hansen, L., B.; Bahl, M., I.; Frandsen, H., L.; Carvalho, V.; Gøbel, R., J.; Dalgaard, M., D.; Plichta, D., R.; Sparholt, M., H.; Vestergaard, H.; Hansen, T.; Sicheritz-Pontén, T.; Nielsen, H., B.; Pedersen, O.; Lauritzen, L.; Kristensen, M.; Gupta, R.; and Licht, T., R.\n\n\n \n\n\n\n Nature Microbiology, 1(9): 1-9. 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut},\n type = {article},\n year = {2016},\n pages = {1-9},\n volume = {1},\n websites = {http://dx.doi.org/10.1038/nmicrobiol.2016.93},\n publisher = {Nature Publishing Group},\n id = {8f66e17a-39b3-37a3-a3ff-a334c5199bc5},\n created = {2025-07-07T13:25:11.419Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:58.865Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Roager2016a},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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.},\n doi = {10.1038/nmicrobiol.2016.93},\n journal = {Nature Microbiology},\n number = {9}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Diet-induced obesity, energy metabolism and gut microbiota in C57BL/6J mice fed Western diets based on lean seafood or lean meat mixtures.\n \n \n \n \n\n\n \n Holm, J., B.; Rønnevik, A.; Tastesen, H., S.; Fjære, E.; Fauske, K., R.; Liisberg, U.; Madsen, L.; Kristiansen, K.; and Liaset, B.\n\n\n \n\n\n\n Journal of Nutritional Biochemistry, 31: 127-136. 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {Diet-induced obesity, energy metabolism and gut microbiota in C57BL/6J mice fed Western diets based on lean seafood or lean meat mixtures},\n type = {article},\n year = {2016},\n keywords = {Dietary protein,Meat,Microbiota,Obesity,Protein source,Seafood,Western diet},\n pages = {127-136},\n volume = {31},\n websites = {http://dx.doi.org/10.1016/j.jnutbio.2015.12.017},\n publisher = {Elsevier Inc.},\n id = {f7759b65-c24c-35f7-8b69-fac66f7c8718},\n created = {2025-07-07T13:25:11.786Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:59.190Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Holm2016},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1016/j.jnutbio.2015.12.017},\n journal = {Journal of Nutritional Biochemistry}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Human gut microbes impact host serum metabolome and insulin sensitivity.\n \n \n \n \n\n\n \n Pedersen, H., K.; Gudmundsdottir, V.; Nielsen, H., B.; Hyotylainen, T.; Nielsen, T.; Jensen, B., A.; Forslund, K.; Hildebrand, F.; Prifti, E.; Falony, G.; Le Chatelier, E.; Levenez, F.; Doré, J.; Mattila, I.; Plichta, D., R.; Pöhö, P.; Hellgren, L., I.; Arumugam, M.; Sunagawa, S.; Vieira-Silva, S.; Jørgensen, T.; Holm, J., B.; Trošt, K.; Kristiansen, K.; Brix, S.; Raes, J.; Wang, J.; Hansen, T.; Bork, P.; Brunak, S.; Oresic, M.; Ehrlich, S., D.; and Pedersen, O.\n\n\n \n\n\n\n Nature, 535(7612): 376-381. 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {Human gut microbes impact host serum metabolome and insulin sensitivity},\n type = {article},\n year = {2016},\n pages = {376-381},\n volume = {535},\n id = {00fa075a-2f80-3580-b77a-3bcd671ddeba},\n created = {2025-07-07T13:25:12.164Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:59.509Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Pedersen2016},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nature18646},\n journal = {Nature},\n number = {7612}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n The Mouse Intestinal Bacterial Collection (miBC) provides host-specific insight into cultured diversity and functional potential of the gut microbiota.\n \n \n \n \n\n\n \n Lagkouvardos, I.; Pukall, R.; Abt, B.; Foesel, B., U.; Meier-Kolthoff, J., P.; Kumar, N.; Bresciani, A.; Martínez, I.; Just, S.; Ziegler, C.; Brugiroux, S.; Garzetti, D.; Wenning, M.; Bui, T., P.; Wang, J.; Hugenholtz, F.; Plugge, C., M.; Peterson, D., A.; Hornef, M., W.; Baines, J., F.; Smidt, H.; Walter, J.; Kristiansen, K.; Nielsen, H., B.; Haller, D.; Overmann, J.; Stecher, B.; and Clavel, T.\n\n\n \n\n\n\n Nature Microbiology, 1(10): 1-15. 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {The Mouse Intestinal Bacterial Collection (miBC) provides host-specific insight into cultured diversity and functional potential of the gut microbiota},\n type = {article},\n year = {2016},\n pages = {1-15},\n volume = {1},\n websites = {http://dx.doi.org/10.1038/nmicrobiol.2016.131},\n publisher = {Nature Publishing Group},\n id = {353d05d3-aa39-3bdb-8430-352888fa2b5d},\n created = {2025-07-07T13:25:12.519Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:59.837Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Lagkouvardos2016},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nmicrobiol.2016.131},\n journal = {Nature Microbiology},\n number = {10}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Transcriptional interactions suggest niche segregation among microorganisms in the human gut.\n \n \n \n \n\n\n \n Plichta, D., R.; Juncker, A., S.; Bertalan, M.; Rettedal, E.; Gautier, L.; Varela, E.; Manichanh, C.; Fouqueray, C.; Levenez, F.; Nielsen, T.; Doré, J.; MacHado, A., M., D.; De Evgrafov, M., C., R.; Hansen, T.; Jørgensen, T.; Bork, P.; Guarner, F.; Pedersen, O.; Sommer, M., O.; Ehrlich, S., D.; Sicheritz-Pontén, T.; Brunak, S.; and Nielsen, H., B.\n\n\n \n\n\n\n Nature Microbiology, 1(August). 2016.\n \n\n\n\n
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\n\n\n@article{\n title = {Transcriptional interactions suggest niche segregation among microorganisms in the human gut},\n type = {article},\n year = {2016},\n volume = {1},\n websites = {http://dx.doi.org/10.1038/nmicrobiol.2016.152},\n publisher = {Nature Publishing Group},\n id = {cb57817b-7e6b-3e04-a8d8-ddd3fbe49c56},\n created = {2025-07-07T13:25:12.873Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:26:00.235Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Plichta2016},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nmicrobiol.2016.152},\n journal = {Nature Microbiology},\n number = {August}\n}\n\n 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.\n
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\n \n \n\n \n \n \n \n \n \n A catalog of the mouse gut metagenome.\n \n \n \n \n\n\n \n Xiao, L.; Feng, Q.; Liang, S.; Sonne, S., B.; Xia, Z.; Qiu, X.; Li, X.; Long, H.; Zhang, J.; Zhang, D.; Liu, C.; Fang, Z.; Chou, J.; Glanville, J.; Hao, Q.; Kotowska, D.; Colding, C.; Licht, T., R.; Wu, D.; Yu, J.; Sung, J., J., Y.; Liang, Q.; Li, J.; Jia, H.; Lan, Z.; Tremaroli, V.; Dworzynski, P.; Nielsen, H., B.; Bäckhed, F.; Doré, J.; Le Chatelier, E.; Ehrlich, S., D.; Lin, J., C.; Arumugam, M.; Wang, J.; Madsen, L.; and Kristiansen, K.\n\n\n \n\n\n\n Nature Biotechnology, 33(10): 1103-1108. 2015.\n \n\n\n\n
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\n\n\n@article{\n title = {A catalog of the mouse gut metagenome},\n type = {article},\n year = {2015},\n pages = {1103-1108},\n volume = {33},\n id = {fb401f33-6e4e-3a9f-9ea0-7fdb191c12e6},\n created = {2025-07-07T13:25:06.720Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:54.555Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Xiao2015},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nbt.3353},\n journal = {Nature Biotechnology},\n number = {10}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n A retrospective metagenomics approach to studying Blastocystis.\n \n \n \n \n\n\n \n Andersen, L., O.; Bonde, I.; Nielsen, H., B., B.; and Stensvold, C., R.\n\n\n \n\n\n\n FEMS Microbiology Ecology, 91(7): 1-9. 2015.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {A retrospective metagenomics approach to studying Blastocystis},\n type = {article},\n year = {2015},\n keywords = {Data mining,Eukaryote,Gut ecology,Microbiota,NGS,Parasite},\n pages = {1-9},\n volume = {91},\n id = {1373d7f5-f843-3a18-99d2-6eae87c7ea7c},\n created = {2025-07-07T13:25:07.071Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:54.948Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Andersen2015},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Andersen, Lee O.Brien and Bonde, Ida and Nielsen, H. B.Henrik Bjørn and Stensvold, Christen Rune},\n doi = {10.1093/femsec/fiv072},\n journal = {FEMS Microbiology Ecology},\n number = {7}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Chronic Trichuris muris Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance of Lactobacilli.\n \n \n \n \n\n\n \n Holm, J., B.; Sorobetea, D.; Kiilerich, P.; Ramayo-Caldas, Y.; Estellé, J.; Ma, T.; Madsen, L.; Kristiansen, K.; and Svensson-Frej, M.\n\n\n \n\n\n\n PloS one, 10(5): e0125495. 1 2015.\n \n\n\n\n
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\n\n\n@article{\n title = {Chronic Trichuris muris Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance of Lactobacilli.},\n type = {article},\n year = {2015},\n pages = {e0125495},\n volume = {10},\n websites = {http://dx.doi.org/10.1371/journal.pone.0125495},\n month = {1},\n day = {5},\n id = {37d69e91-6eff-34ba-89d2-205a9910287c},\n created = {2025-07-07T13:25:07.456Z},\n accessed = {2015-05-13},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:55.291Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Holm2015},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1371/journal.pone.0125495},\n journal = {PloS one},\n number = {5}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota.\n \n \n \n \n\n\n \n Forslund, K.; Hildebrand, F.; Nielsen, T.; Falony, G.; Le Chatelier, E.; Sunagawa, S.; Prifti, E.; Vieira-Silva, S.; Gudmundsdottir, V.; Krogh Pedersen, H.; Arumugam, M.; Kristiansen, K.; Yvonne Voigt, A.; Vestergaard, H.; Hercog, R.; Igor Costea, P.; Roat Kultima, J.; Li, J.; Jørgensen, T.; Levenez, F.; Dore, J.; Bjørn Nielsen, H.; Brunak, S.; Raes, J.; Hansen, T.; Wang, J.; Dusko Ehrlich, S.; Bork, P.; and Pedersen, O.\n\n\n \n\n\n\n Nature, 528(7581): 262-266. 2015.\n \n\n\n\n
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\n\n\n@article{\n title = {Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota},\n type = {article},\n year = {2015},\n pages = {262-266},\n volume = {528},\n websites = {http://dx.doi.org/10.1038/nature15766},\n publisher = {Nature Publishing Group},\n id = {42e3e109-8290-3871-80fe-ff4b77c3df3d},\n created = {2025-07-07T13:25:07.809Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:55.622Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n citation_key = {Forslund2015},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nature15766},\n journal = {Nature},\n number = {7581}\n}\n\n 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.\n
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\n \n \n\n \n \n \n \n \n \n An integrated catalog of reference genes in the human gut microbiome.\n \n \n \n \n\n\n \n Li, J.; Wang, J.; Jia, H.; Cai, X.; Zhong, H.; Feng, Q.; Sunagawa, S.; Arumugam, M.; Kultima, J., R.; Prifti, E.; Nielsen, T.; Juncker, A., S.; Manichanh, C.; Chen, B.; Zhang, W.; Levenez, F.; Wang, J.; Xu, X.; Xiao, L.; Liang, S.; Zhang, D.; Zhang, Z.; Chen, W.; Zhao, H.; Al-Aama, J., Y.; Edris, S.; Yang, H.; Wang, J.; Hansen, T.; Nielsen, H., B.; Brunak, S.; Kristiansen, K.; Guarner, F.; Pedersen, O.; Doré, J.; Ehrlich, S., D.; and Bork, P.\n\n\n \n\n\n\n Nature Biotechnology, 32(8): 834-841. 2014.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
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Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n\n
\n\n\n@article{\n title = {An integrated catalog of reference genes in the human gut microbiome},\n type = {article},\n year = {2014},\n pages = {834-841},\n volume = {32},\n id = {a0e09caa-21ea-3246-898e-e25bb46dab51},\n created = {2025-07-07T13:25:05.931Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:53.746Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nbt.2942},\n journal = {Nature Biotechnology},\n number = {8}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes.\n \n \n \n \n\n\n \n Nielsen, H., B.; Almeida, M.; Juncker, A., S.; Rasmussen, S.; Li, J.; Sunagawa, S.; Plichta, D., R.; Gautier, L.; Pedersen, A., G.; Le Chatelier, E.; Pelletier, E.; Bonde, I.; Nielsen, T.; Manichanh, C.; Arumugam, M.; Batto, J.; Quintanilha Dos Santos, M., B.; Blom, N.; Borruel, N.; Burgdorf, K., S.; Boumezbeur, F.; Casellas, F.; Doré, J.; Dworzynski, P.; Guarner, F.; Hansen, T.; Hildebrand, F.; Kaas, R., S.; Kennedy, S.; Kristiansen, K.; Kultima, J., R.; Léonard, P.; Levenez, F.; Lund, O.; Moumen, B.; Le Paslier, D.; Pons, N.; Pedersen, O.; Prifti, E.; Qin, J.; Raes, J.; Sørensen, S.; Tap, J.; Tims, S.; Ussery, D., W.; Yamada, T.; Renault, P.; Sicheritz-Ponten, T.; Bork, P.; Wang, J.; Brunak, S.; and Ehrlich, S., D.\n\n\n \n\n\n\n Nature biotechnology, 32(8): 822-828. 2014.\n \n\n\n\n
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\n\n\n@article{\n title = {Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes.},\n type = {article},\n year = {2014},\n pages = {822-828},\n volume = {32},\n websites = {http://dx.doi.org/10.1038/nbt.2939\\nhttp://www.cbs.dtu.dk/databases/CAG/},\n id = {c35750dd-7d48-3219-bc0e-7dbb34830f04},\n created = {2025-07-07T13:25:06.339Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:54.131Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nbt.2939},\n journal = {Nature biotechnology},\n number = {8}\n}\n\n 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.\n
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\n \n \n\n \n \n \n \n \n \n Metagenomic species profiling using universal phylogenetic marker genes.\n \n \n \n \n\n\n \n Sunagawa, S.; Mende, D., R.; Zeller, G.; Izquierdo-Carrasco, F.; Berger, S., A.; Kultima, J., R.; Coelho, L., P.; Arumugam, M.; Tap, J.; Nielsen, H., B.; Rasmussen, S.; Brunak, S.; Pedersen, O.; Guarner, F.; De Vos, W., M.; Wang, J.; Li, J.; Doré, J.; Dusko Ehrlich, S.; Stamatakis, A.; and Bork, P.\n\n\n \n\n\n\n Nature Methods, 10(12): 1196-1199. 2013.\n \n\n\n\n
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\n\n\n@article{\n title = {Metagenomic species profiling using universal phylogenetic marker genes},\n type = {article},\n year = {2013},\n pages = {1196-1199},\n volume = {10},\n id = {52098d3a-bc60-3955-9662-ed6dfc4b200c},\n created = {2025-07-07T13:25:04.758Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:52.790Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nmeth.2693},\n journal = {Nature Methods},\n number = {12}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n Richness of human gut microbiome correlates with metabolic markers.\n \n \n \n \n\n\n \n Le Chatelier, E.; Nielsen, T.; Qin, J.; Prifti, E.; Hildebrand, F.; Falony, G.; Almeida, M.; Arumugam, M.; Batto, J.; Kennedy, S.; Leonard, P.; Li, J.; Burgdorf, K.; Grarup, N.; Jørgensen, T.; Brandslund, I.; Nielsen, H., B.; Juncker, A., S.; Bertalan, M.; Levenez, F.; Pons, N.; Rasmussen, S.; Sunagawa, S.; Tap, J.; Tims, S.; Zoetendal, E., G.; Brunak, S.; Clément, K.; Doré, J.; Kleerebezem, M.; Kristiansen, K.; Renault, P.; Sicheritz-Ponten, T.; de Vos, W., M.; Zucker, J.; Raes, J.; Hansen, T.; Bork, P.; Wang, J.; Ehrlich, S., D.; Pedersen, O.; Guedon, E.; Delorme, C.; Layec, S.; Khaci, G.; van de Guchte, M.; Vandemeulebrouck, G.; Jamet, A.; Dervyn, R.; Sanchez, N.; Maguin, E.; Haimet, F.; Winogradski, Y.; Cultrone, A.; Leclerc, M.; Juste, C.; Blottière, H.; Pelletier, E.; LePaslier, D.; Artiguenave, F.; Bruls, T.; Weissenbach, J.; Turner, K.; Parkhill, J.; Antolin, M.; Manichanh, C.; Casellas, F.; Boruel, N.; Varela, E.; Torrejon, A.; Guarner, F.; Denariaz, G.; Derrien, M.; van Hylckama Vlieg, J., E., T.; Veiga, P.; Oozeer, R.; Knol, J.; Rescigno, M.; Brechot, C.; M'Rini, C.; Mérieux, A.; and Yamada, T.\n\n\n \n\n\n\n Nature, 500(7464): 541-6. 8 2013.\n \n\n\n\n
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Paper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n\n
\n\n\n@article{\n title = {Richness of human gut microbiome correlates with metabolic markers.},\n type = {article},\n year = {2013},\n 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},\n pages = {541-6},\n volume = {500},\n websites = {http://www.ncbi.nlm.nih.gov/pubmed/23985870},\n month = {8},\n day = {29},\n id = {ff53eeab-0e60-3cc3-816e-c2b4ff3fcbe0},\n created = {2025-07-07T13:25:05.209Z},\n accessed = {2013-10-17},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:53.092Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nature12506},\n journal = {Nature},\n number = {7464}\n}\n\n 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.\n
\n\n\n\n \n\n \n \n \n \n \n \n The chemical interactome space between the human host and the genetically defined gut metabotypes.\n \n \n \n \n\n\n \n Jacobsen, U., P.; Nielsen, H., B.; Hildebrand, F.; Raes, J.; Sicheritz-Ponten, T.; Kouskoumvekaki, I.; and Panagiotou, G.\n\n\n \n\n\n\n ISME Journal, 7(4): 730-742. 2013.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n\n\n\n
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\n\n\n@article{\n title = {The chemical interactome space between the human host and the genetically defined gut metabotypes},\n type = {article},\n year = {2013},\n keywords = {microbiome; metabolic network; drugs; protein inte},\n pages = {730-742},\n volume = {7},\n id = {40ec2558-926a-3d25-bf3d-b2ef1c166313},\n created = {2025-07-07T13:25:05.569Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:53.425Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n author = {Jacobsen, Ulrik Plesner and Nielsen, Henrik Bjorn and Hildebrand, Falk and Raes, Jeroen and Sicheritz-Ponten, Thomas and Kouskoumvekaki, Irene and Panagiotou, Gianni},\n doi = {10.1038/ismej.2012.141},\n journal = {ISME Journal},\n number = {4}\n}\n\n 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.\n
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\n\n \n \n 2012\n \n \n (1)\n \n \n
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\n \n \n\n \n \n \n \n \n \n A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus) and humans (Homo sapiens).\n \n \n \n \n\n\n \n Hildebrand, F.; Ebersbach, T.; Nielsen, H.; Li, X.; Sonne, S.; Bertalan, M.; Dimitrov, P.; Madsen, L.; Qin, J.; Wang, J.; Raes, J.; Kristiansen, K.; and Licht, T.\n\n\n \n\n\n\n BMC Genomics, 13(1): 514. 2012.\n \n\n\n\n
\n\n\n\n \n \nPaper\n \n \n \n Website\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n
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\n\n\n@article{\n title = {A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus) and humans (Homo sapiens)},\n type = {article},\n year = {2012},\n pages = {514},\n volume = {13},\n websites = {BMC Genomics},\n publisher = {BMC Genomics},\n id = {8a93a304-b49f-3cf2-bb6e-571fa847c61b},\n created = {2025-07-07T13:25:04.407Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:52.457Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1186/1471-2164-13-514},\n journal = {BMC Genomics},\n number = {1}\n}\n\n 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.\n
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\n\n \n \n 2011\n \n \n (1)\n \n \n
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\n \n \n\n \n \n \n \n \n \n Enterotypes of the human gut microbiome.\n \n \n \n \n\n\n \n Arumugam, M.; Raes, J.; Pelletier, E.; Le Paslier, D.; Yamada, T.; Mende, D., R.; Fernandes, G., R.; Tap, J.; Bruls, T.; Batto, J.; Bertalan, M.; Borruel, N.; Casellas, F.; Fernandez, L.; Gautier, L.; Hansen, T.; Hattori, M.; Hayashi, T.; Kleerebezem, M.; Kurokawa, K.; Leclerc, M.; Levenez, F.; Manichanh, C.; Nielsen, H., B.; Nielsen, T.; Pons, N.; Poulain, J.; Qin, J.; Sicheritz-Ponten, T.; Tims, S.; Torrents, D.; Ugarte, E.; Zoetendal, E., G.; Wang, J.; Guarner, F.; Pedersen, O.; de Vos, W., M.; Brunak, S.; Doré, J.; Antolín, M.; Artiguenave, F.; Blottiere, H., M.; Almeida, M.; Brechot, C.; Cara, C.; Chervaux, C.; Cultrone, A.; Delorme, C.; Denariaz, G.; Dervyn, R.; Foerstner, K., U.; Friss, C.; van de Guchte, M.; Guedon, E.; Haimet, F.; Huber, W.; van Hylckama-Vlieg, J.; Jamet, A.; Juste, C.; Kaci, G.; Knol, J.; Lakhdari, O.; Layec, S.; Le Roux, K.; Maguin, E.; Mérieux, A.; Melo Minardi, R.; M'rini, C.; Muller, J.; Oozeer, R.; Parkhill, J.; Renault, P.; Rescigno, M.; Sanchez, N.; Sunagawa, S.; Torrejon, A.; Turner, K.; Vandemeulebrouck, G.; Varela, E.; Winogradsky, Y.; Zeller, G.; Weissenbach, J.; Ehrlich, S., D.; and Bork, P.\n\n\n \n\n\n\n Nature, 473(7346): 174-180. 2011.\n \n\n\n\n
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\n\n\n@article{\n title = {Enterotypes of the human gut microbiome.},\n type = {article},\n year = {2011},\n pages = {174-180},\n volume = {473},\n id = {0041b61a-723c-3991-b174-22a33b01ef15},\n created = {2025-07-07T13:25:04.040Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:52.100Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nature10187},\n journal = {Nature},\n number = {7346}\n}\n\n 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.\n
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\n\n\n\n\n \n \n 2010\n \n \n (1)\n \n \n
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\n \n \n\n \n \n \n \n \n \n A human gut microbial gene catalogue established by metagenomic sequencing.\n \n \n \n \n\n\n \n Qin, J.; Li, R.; Raes, J.; Arumugam, M.; Burgdorf, K., S.; Manichanh, C.; Nielsen, T.; Pons, N.; Levenez, F.; Yamada, T.; Mende, D., R.; Li, J.; Xu, J.; Li, S.; Li, D.; Cao, J.; Wang, B.; Liang, H.; Zheng, H.; Xie, Y.; Tap, J.; Lepage, P.; Bertalan, M.; Batto, J., M.; Hansen, T.; Le Paslier, D.; Linneberg, A.; Nielsen, H., B.; Pelletier, E.; Renault, P.; Sicheritz-Ponten, T.; Turner, K.; Zhu, H.; Yu, C.; Li, S.; Jian, M.; Zhou, Y.; Li, Y.; Zhang, X.; Li, S.; Qin, N.; Yang, H.; Wang, J.; Brunak, S.; Doré, J.; Guarner, F.; Kristiansen, K.; Pedersen, O.; Parkhill, J.; Weissenbach, J.; Bork, P.; Ehrlich, S., D.; Wang, J.; Antolin, M.; Artiguenave, F.; Blottiere, H.; Borruel, N.; Bruls, T.; Casellas, F.; Chervaux, C.; Cultrone, A.; Delorme, C.; Denariaz, G.; Dervyn, R.; Forte, M.; Friss, C.; Van De Guchte, M.; Guedon, E.; Haimet, F.; Jamet, A.; Juste, C.; Kaci, G.; Kleerebezem, M.; Knol, J.; Kristensen, M.; Layec, S.; Le Roux, K.; Leclerc, M.; Maguin, E.; Melo Minardi, R.; Oozeer, R.; Rescigno, M.; Sanchez, N.; Tims, S.; Torrejon, T.; Varela, E.; De Vos, W.; Winogradsky, Y.; and Zoetendal, E.\n\n\n \n\n\n\n Nature, 464(7285): 59-65. 2010.\n \n\n\n\n
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\n\n\n@article{\n title = {A human gut microbial gene catalogue established by metagenomic sequencing},\n type = {article},\n year = {2010},\n pages = {59-65},\n volume = {464},\n id = {0ec10282-10aa-3437-a5a9-ce5815749e6f},\n created = {2025-07-07T13:25:03.553Z},\n file_attached = {true},\n profile_id = {9c1a206b-6cfb-375e-a257-a4c31f5a0791},\n group_id = {89bece75-0a7e-3035-98e1-71b82260b8e8},\n last_modified = {2025-07-07T13:25:51.745Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {true},\n hidden = {false},\n private_publication = {false},\n 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.},\n bibtype = {article},\n 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},\n doi = {10.1038/nature08821},\n journal = {Nature},\n number = {7285}\n}\n\n 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.\n
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