Browsing by Subject "Gastrointestinal Microbiome"

Now showing 1 - 3 of 3
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    Gut microbiota regulates K/BxN autoimmune arthritis through Tfh but not Th17 cells
    (American Association of Immunologists, 2016-02-15) Block, Katharine E.; Zheng, Zhong; Dent, Alexander L.; Kee, Barbara L.; Huang, Haochu; Department of Microbiology & Immunology, IU School of Medicine
    The bacterial community that colonizes mucosal surfaces helps shape the development and function of the immune system. The K/BxN autoimmune arthritis model is dependent on the microbiota, and particularly on segmented filamentous bacteria, for the autoimmune phenotype. The mechanisms of how the gut microbiota affects arthritis development are not well understood. In this study, we investigate the contribution of two T cell subsets, Th17 and follicular helper T (Tfh), to arthritis and how microbiota modulates their differentiation. Using genetic approaches, we demonstrate that IL-17 is dispensable for arthritis. Antibiotic treatment inhibits disease in IL-17-deficient animals, suggesting that the gut microbiota regulates arthritis independent of Th17 cells. In contrast, conditional deletion of Bcl6 in T cells blocks Tfh cell differentiation and arthritis development. Furthermore, Tfh cell differentiation is defective in antibiotic-treated mice. Taken together, we conclude that gut microbiota regulates arthritis through Tfh but not Th17 cells. These findings have implications in our understanding of how environmental factors contribute to the development of autoimmune diseases.
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    Microbial nitrogen limitation in the mammalian large intestine
    (Springer Nature, 2018-12) Reese, Aspen T.; Pereira, Fátima C.; Schintlmeister, Arno; Berry, David; Wagner, Michael; Hale, Laura P.; Wu, Anchi; Jiang, Sharon; Durand, Heather K.; Zhou, Xiyou; Premont, Richard T.; Diehl, Anna Mae; O'Connell, Thomas M.; Alberts, Susan C.; Kartzinel, Tyler R.; Pringle, Robert M.; Dunn, Robert R.; Wright, Justin P.; David, Lawrence A.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Resource limitation is a fundamental factor governing the composition and function of ecological communities. However, the role of resource supply in structuring the intestinal microbiome has not been established and represents a challenge for mammals that rely on microbial symbionts for digestion: too little supply might starve the microbiome while too much might starve the host. We present evidence that microbiota occupy a habitat that is limited in total nitrogen supply within the large intestines of 30 mammal species. Lowering dietary protein levels in mice reduced their faecal concentrations of bacteria. A gradient of stoichiometry along the length of the gut was consistent with the hypothesis that intestinal nitrogen limitation results from host absorption of dietary nutrients. Nitrogen availability is also likely to be shaped by host-microbe interactions: levels of host-secreted nitrogen were altered in germ-free mice and when bacterial loads were reduced via experimental antibiotic treatment. Single-cell spectrometry revealed that members of the phylum Bacteroidetes consumed nitrogen in the large intestine more readily than other commensal taxa did. Our findings support a model where nitrogen limitation arises from preferential host use of dietary nutrients. We speculate that this resource limitation could enable hosts to regulate microbial communities in the large intestine. Commensal microbiota may have adapted to nitrogen-limited settings, suggesting one reason why excess dietary protein has been associated with degraded gut-microbial ecosystems.
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    Trans-omic knowledge transfer modeling infers gut microbiome biomarkers of anti-TNF resistance in ulcerative colitis
    (World Scientific, 2023) Trinh, Alan; Ran, Ran; Brubaker, Douglas K
    A critical challenge in analyzing multi-omics data from clinical cohorts is the re-use of these valuable datasets to answer biological questions beyond the scope of the original study. Transfer Learning and Knowledge Transfer approaches are machine learning methods that leverage knowledge gained in one domain to solve a problem in another. Here, we address the challenge of developing Knowledge Transfer approaches to map trans-omic information from a multi-omic clinical cohort to another cohort in which a novel phenotype is measured. Our test case is that of predicting gut microbiome and gut metabolite biomarkers of resistance to anti-TNF therapy in Ulcerative Colitis patients. Three approaches are proposed for Trans-omic Knowledge Transfer, and the resulting performance and downstream inferred biomarkers are compared to identify efficacious methods. We find that multiple approaches reveal similar metabolite and microbial biomarkers of anti-TNF resistance and that these commonly implicated biomarkers can be validated in literature analysis. Overall, we demonstrate a promising approach to maximize the value of the investment in large clinical multi-omics studies by re-using these data to answer biological and clinical questions not posed in the original study.