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Publication

Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice.

Immunity | 2019

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.

Pubmed ID: 30650377 RIS Download

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Associated grants

Agency: NCI NIH HHS, United States
Id: P30 CA016087
Agency: NCI NIH HHS, United States
Id: R01 CA190400
Agency: NIDDK NIH HHS, United States
Id: F30 DK108487
Agency: NCATS NIH HHS, United States
Id: UL1 TR000124
Agency: NCI NIH HHS, United States
Id: P30 CA016042
Agency: NIGMS NIH HHS, United States
Id: R01 GM108505
Agency: NIDDK NIH HHS, United States
Id: F31 DK112679
Agency: NIAID NIH HHS, United States
Id: U24 AI118644
Agency: NIDDK NIH HHS, United States
Id: P30 DK041301
Agency: NIDDK NIH HHS, United States
Id: R01 DK085691
Agency: NIDDK NIH HHS, United States
Id: P01 DK046763
Agency: NCCIH NIH HHS, United States
Id: P50 AT008661

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