Cell Host & Microbe
Volume 9, Issue 5, 19 May 2011, Pages 390-403
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Article
Commensal Bacteroides Species Induce Colitis in Host-Genotype-Specific Fashion in a Mouse Model of Inflammatory Bowel Disease

https://doi.org/10.1016/j.chom.2011.04.009Get rights and content
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Summary

The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here, we fulfilled Koch's postulates in host-genotype-specific fashion using a mouse model of IBD with human-relevant disease-susceptibility mutations. From screening experiments we isolated common commensal Bacteroides species, introduced them into antibiotic-pretreated mice, and quantitatively reisolated them in culture. The bacteria colonized IBD-susceptible and -nonsusceptible mice equivalently, but induced disease exclusively in susceptible animals. Conversely, commensal Enterobacteriaceae were >100-fold enriched during spontaneous disease, but an Enterobacteriaceae isolate failed to induce disease in antibiotic-pretreated mice despite robust colonization. We thus demonstrate that IBD-associated microbiota alterations do not necessarily reflect underlying disease etiology. These findings establish important experimental criteria and a conceptual framework for understanding microbial contributions to IBD.

Highlights

► A screen for disease-inducing bacteria in a non-germ-free, genetic model of IBD ► Common commensal Bacteroides fulfill host-genotype-specific Koch's postulates for IBD ► Commensal Enterobacteriaceae are enriched during spontaneous disease ► Enterobacteriaceae not sufficient to induce disease despite robust colonization

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