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 Jan 15;50(1):212-224.e4. doi: 10.1016/j.immuni.2018.12.015.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Colitis / chemically induced
  • Colitis / immunology
  • Colitis / microbiology*
  • Disease Models, Animal
  • Disease Progression
  • Gastrointestinal Microbiome / genetics*
  • Homeostasis
  • Humans
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / microbiology*
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • RNA, Ribosomal, 16S / genetics*
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / metabolism*


  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Ribosomal, 16S