@article{9cc8a86d39834007ba9479074e209497,
title = "Defined microbiota transplant restores Th17/RORγt+ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas",
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 (IBDs), where clinical trials of fecal microbiota transplantation 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, a deficit in the tolerogenic RORγt+ regulatory T (Treg) cell subset, and susceptibility to disease in colitis models. Transplanting healthy donor-derived microbiotas into mice colonized with human IBD microbiotas led 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{\textquoteright}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, which was correlated with a reduction in Th17 cells and protection from colitis.",
keywords = "Fecal microbiota transplant, Microbiome, Mucosal immunology, Regulatory T cells, Th17 cells",
author = "Britton, {Graham J.} and Contijoch, {Eduardo J.} and Spindler, {Matthew P.} and Varun Aggarwala and Belgin Dogan and Gerold Bongers and Mateo, {Lani San} and Andrew Baltus and Anuk Das and Dirk Gevers and Borody, {Thomas J.} and Kaakoush, {Nadeem O.} and Kamm, {Michael A.} and Hazel Mitchell and Sudarshan Paramsothy and Clemente, {Jose C.} and Colombel, {Jean Frederic} and Simpson, {Kenneth W.} and Dubinsky, {Marla C.} and Ari Grinspan and Faith, {Jeremiah J.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank C. Fermin, E. Vazquez, and G. N. Escano (Mount Sinai Immunology Institute Gnotobiotic Facility) and E. Ariztia, O. Vennaro, I. Mogno, and Z. Li for technical support. This work was supported in part by the staff and resources of Scientific Computing and of the Flow Cytometry Core at the Icahn School of Medicine at Mount Sinai. G.J.B. is supported by a Research Fellowship Award from the Crohn{\textquoteright}s and Colitis Foundation of America (CCFA). This work was further supported by NIH National Institute of General Medical Sciences Grant GM108505 and National Institute of Diabetes and Digestive Diseases Grants DK112978 and DK124133; the Janssen Human Microbiome Institute; a CCFA Microbiome Innovation Award (362048); the New York Crohn{\textquoteright}s Foundation (J.J.F.); NIH Grants DK112679 (to E.J.C.) and AI078892 (to M.P.S.); and a CCFA Research Fellowship Award (to V.A.). Next-generation sequencing was performed at the New York University School of Medicine by the Genome Technology Center that is partially supported by Cancer Center Support Grant P30CA016087. Funding Information: We thank C. Fermin, E. Vazquez, and G. N. Escano (Mount Sinai Immunology Institute Gnotobiotic Facility) and E. Ariztia, O. Vennaro, I. Mogno, and Z. Li for technical support. This work was supported in part by the staff and resources of Scientific Computing and of the Flow Cytometry Core at the Icahn School of Medicine at Mount Sinai. G.J.B. is supported by a Research Fellowship Award from the Crohn?s and Colitis Foundation of America (CCFA). This work was further supported by NIH National Institute of General Medical Sciences Grant GM108505 and National Institute of Diabetes and Digestive Diseases Grants DK112978 and DK124133; the Janssen Human Microbiome Institute; a CCFA Microbiome Innovation Award (362048); the New York Crohn?s Foundation (J.J.F.); NIH Grants DK112679 (to E.J.C.) and AI078892 (to M.P.S.); and a CCFA Research Fellowship Award (to V.A.). Next-generation sequencing was performed at the New York University School of Medicine by the Genome Technology Center that is partially supported by Cancer Center Support Grant P30CA016087. Publisher Copyright: {\textcopyright} 2020 National Academy of Sciences. All rights reserved.",
year = "2020",
month = sep,
day = "1",
doi = "10.1073/pnas.1922189117",
language = "English",
volume = "117",
pages = "21536--21545",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "35",
}