Inflammatory bowel disease microbiotas alter gut CD4 T-cell homeostasis and drive colitis in mice
Graham J Britton,
Eduardo J. Contijoch,
Olivia H Vennaro,
Sean R. Llewellyn,
Dermot P.B. McGovern,
Jonathan P. Jacobs,
Jose C. Clemente,
Marla C Dubinsky,
Jeremiah J Faith
Posted 06 Mar 2018
bioRxiv DOI: 10.1101/276774
Posted 06 Mar 2018
To examine the functional contribution of Inflammatory Bowel Disease (IBD) microbes to immune homeostasis and colitis, we colonized unchallenged and colitis-susceptible germ-free mice with over twenty human intestinal microbiotas from healthy and IBD donors. Compared to healthy microbiotas, IBD microbiotas led to expanded RORgammat+Th17 cells and reduced RORgammat+Treg in the gut of unchallenged gnotobiotic mice and increased disease severity in colitis-susceptible mice. The proportions of RORgammat+Th17 and RORgammat+Treg induced by each microbiota were highly predictive of the human disease status and strongly correlated with disease severity in colitis-susceptible mice colonized with the same human microbiotas. The transmittable functional potential of IBD microbes suggests a mechanism for a microbial contribution to IBD pathogenesis and a potential route for its treatment and prevention.
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