@article{24d11fa7d02640b089c38adfb58f90fd,
title = "Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice",
abstract = "Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of RORγt+ Treg cells. Colonization with IBD microbiotas exacerbated disease in a model where colitis is induced upon transfer of naive T cells into Rag1−/− mice. The proportions of Th17 and RORγt+ Treg cells induced by each microbiota were predictive of human disease status and accounted for disease severity in the Rag1−/− colitis model. Thus, an impact on intestinal Th17 and RORγt+ Treg cell compartments emerges as a unifying feature of IBD microbiotas, suggesting a general mechanism for microbial contribution to IBD pathogenesis.",
author = "Britton, {Graham J.} and Contijoch, {Eduardo J.} and Ilaria Mogno and Vennaro, {Olivia H.} and Llewellyn, {Sean R.} and Ruby Ng and Zhihua Li and Arthur Mortha and Miriam Merad and Anuk Das and Dirk Gevers and McGovern, {Dermot P.B.} and Namita Singh and Jonathan Braun and Jacobs, {Jonathan P.} and Clemente, {Jose C.} and Ari Grinspan and Sands, {Bruce E.} and Colombel, {Jean Frederic} and Dubinsky, {Marla C.} and Faith, {Jeremiah J.}",
note = "Funding Information: We thank C. Fermin, E. Vazquez, and G.N. Escano of the Mount Sinai Immunology Institute Gnotobiotic Facility for technical support. This work was supported by grants from the NIH (NIGMS GM108505 and NCCIH AT008661), Janssen Human Microbiome Institute, CCFA Microbiome Innovation Award (362048), and the New York Crohn's Foundation to J.J.F., NIH DK108487 to S.R.L., NIH DK112679 to E.J.C., and NIH DK085691, CA016042, and UL1TR000124 to J.B. G.J.B. is supported by a Research Fellowship Award from the Crohn's and Colitis Foundation of America. Next-generation sequencing was performed at NYU School of Medicine by the Genome Technology Center partially supported by the Cancer Center Support Grant, P30CA016087. 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. Funding Information: We thank C. Fermin, E. Vazquez, and G.N. Escano of the Mount Sinai Immunology Institute Gnotobiotic Facility for technical support. This work was supported by grants from the NIH ( NIGMS GM108505 and NCCIH AT008661 ), Janssen Human Microbiome Institute , CCFA Microbiome Innovation Award ( 362048 ), and the New York Crohn{\textquoteright}s Foundation to J.J.F., NIH DK108487 to S.R.L., NIH DK112679 to E.J.C., and NIH DK085691 , CA016042 , and UL1TR000124 to J.B. G.J.B. is supported by a Research Fellowship Award from the Crohn's and Colitis Foundation of America . Next-generation sequencing was performed at NYU School of Medicine by the Genome Technology Center partially supported by the Cancer Center Support Grant, P30CA016087 . 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. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2019",
month = jan,
day = "15",
doi = "10.1016/j.immuni.2018.12.015",
language = "English",
volume = "50",
pages = "212--224.e4",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "1",
}