Defined microbiota transplant restores Th17/RORγt + regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas
Year: 2020
Type: article
Abstract: The building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases, where clinical trials of fecal microbiota transplant have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells and a deficit in the tolerogenic RORγt + Treg cell subset. Transplanting healthy donor-derived microbiota into mice colonized with human IBD microbiotas lead to induction of RORγt + Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohn’s disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, correlated with a reduction in Th17 cells.
Authors: Graham J. Britton, Eduardo J. Contijoch, Matthew P. Spindler, Varun Aggarwala, Belgin Dogan, Gerold Bongers, Lani San Mateo, Andrew Baltus, Anuk Das, Dirk Gevers, Thomas J. Borody, Nadeem O. Kaakoush, Michael A. Kamm, Hazel Mitchell, Sudarshan Paramsothy, Jose C. Clemente, Jean-Frederic Colombel, Kenneth W. Simpson, Marla C. Dubinsky, Ari Grinspan, Jeremiah J. Faith
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: Crohn's and Colitis Foundation of America, Icahn School of Medicine at Mount Sinai, Crohn's and Colitis Foundation, York University, National Institutes of Health, School of Medicine, New York University, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Janssen Research and Development
Awards: G1911494126, Decoding mutualistic microbiota-B cell interactions in the HIV-1-infected gut: impact on immunological non-responders, G2617526763, G2621239591, The relationship between host diet, the gut microbiota, and host transcription, UCLA Clinical and Translational Science Institute, The effects of diet and the microbiota in determining host health, G3842773543, G40778190, Big Omics Data Engine 2 Supercomputer, G4610885380, G506511048, G5405525085, The impact of HIV-1 infection and its treatment on gastrointestinal B cells, G6921960464, G7800188239, G7912149278, Improving Fecal Microbiota Transplantation Engraftment and Efficacy, G8047817453, G8812770837, G9000261587, Uncovering the rules of gut microbiome strain transmission, Colon O-glycosylated mucus in the homeostasis of microbiota and host, The Influence Of Gut Microbiota Stability In Inflammatory Bowel Disease, Cancer Center Support Grant, Translational Immunology Training Program
OpenAlex ID: W3057557785