Enterobacteriaceae Act in Concert with the Gut Microbiota to Induce Spontaneous and Maternally Transmitted Colitis

Abstract

SUMMARY In inflammatory bowel disease, the relationship between a host and gut microbial community goes awry. We have characterized the fecal microbial communities in a mouse IBD model driven by T-bet deficiency in the innate immune system. 16S rRNA-based analysis of T-bet−/− × Rag2−/− and Rag2−/− mice revealed distinctive communities that correlate with host genotype. Culture-based surveys, invasion assays, antibiotic treatment, and TNF-α blockade disclosed that the presence of Klebsiella pneumoniae and Proteus mirabilis correlates with colitis in T-bet−/− × Rag2−/− animals, and that T-bet−/− × Rag2−/− derived strains can elicit colitis in Rag2−/− and wild-type adults. Cross-fostering experiments provided evidence for the role of these organisms in maternal transmission of disease. This model provides a foundation for defining how gut microbial communities work in concert with specific culturable colitogenic agents to cause IBD, and a foundation for conducting proof-of-concept tests of new preventative or therapeutic measures directed at components of the gut microbiota and/or host.

The dual oxidase gene BdDuox regulates the intestinal bacterial community homeostasis of Bactrocera dorsalis

“…In this line, conditionally pathogenic autochthonous bacteria (that is, pathobionts such as Gluconobacter morbifer) of Drosophila are normally quiescent but are able to provoke chronic inflammation under dysbiosis conditions, as observed in Caudal-deficient Drosophila (Ryu et al, 2008). The intestinal dysbiosis caused by the disruption of intestinal bacterial community are reminiscent of inflammatory bowel diseases, wherein some previously commensal resident bacteria cause gut pathology under certain condition (Garrett et al, 2010;Sokol and Seksik, 2010).…”

Intestinal Microbes in Inflammatory Bowel Diseases

“…Moreover, intestinal epithelial-specifi c defects in Toll-like receptor and nuclear factor-κ B signaling can lead to mucosal barrier defects, mucosal luminal bacterial translocation, and immune-mediated intestinal infl ammation ( 45 ). Finally, a primary etiologic role for intestinal dysbiosis is supported by transmission of colitis with fecal transplant ( 46,47 ).…”

Exploring host–microbiota interactions in animal models and humans

“…Mouse models of colitis, including FVB.mdr1a À/À (Nones et al 2009), BALB/c.T-bet À/À 3 RAG2 À/À (Garrett et al 2010a) and IL-10R2 À/À 3 TGFBRII À/À (Bloom et al 2011) mice, have been profiled using multiple methodologies inclusive of culture-dependent and -independent techniques and revealed distinctive patterns with the gut microbiota. The Enterobacteriaceae Klebsiella pneumoniae and Proteus mirabilis were associated with colitis in T-bet À/À 3 RAG2 À/À mice (Garrett et al 2010a), while Bacteroides thetaiotaomicron was associated with disease in IL-10R2 À/À 3 TGFBRII À/À mice (Bloom et al 2011), suggesting that a variety of genes may impact colonization and fitness of specific gut microbes in the setting of an inflamed epithelium and genetic immune perturbations. Mice provide significant opportunities in GWAS (genome-wide association studies) and MWAS (microbiome-wide association studies) to interrogate the contribution of genetic risk alleles to disease phenotype and the presence of genetic risk alleles to microbiome patterns.…”