Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease

Seth M. Bloom, Vinieth N. Bijanki, Gerardo M. Nava, Lulu Sun, Nicole P. Malvin, David L. Donermeyer, W. Michael Dunne, Paul M. Allen, Thaddeus S. Stappenbeck

Research output: Contribution to journalArticlepeer-review

327 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)390-403
Number of pages14
JournalCell Host and Microbe
Volume9
Issue number5
DOIs
StatePublished - May 19 2011

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