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

https://www.cell.com/immunity/fulltext/S1074-7613(18)30563-6

Highlights

  • Fecal microbiotas from humans with IBD alter gut CD4 + T cell homeostasis in mice
  • Microbiotas from individuals with IBD induce more Th2 and Th17 cells
  • Microbiotas from healthy individuals induce more RORgt + Treg cells
  • In a model of colitis, mice colonized with IBD microbiotas get more severe disease

Summary

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.

Graphical Abstract

Figure thumbnail fx1

mice84685

99

888

00

2224455666777

blog8456854blog777

111

uuu

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s