Intestinal Bacterial Composition of Lymphopenic Mice and Susceptibility to CD45RBhigh T Cell-Induced Colitis

Abstract

Background Following relocation to our current institution we observed a 40% reduction in the incidence of T cell-induced colitis in our well-established mouse model of IBD. The objectives of this study were to: a) quantify and compare the colonic microbiota in healthy and colitic mice obtained from our current (TTUHSC) and former insitution (LSUHSC), and b) determine whether colonization of healthy mice housed at our current institution with feces from healthy or colitic mice from LSUHSC alters the incidence and/or severity of colitis. Methods DNA from frozen feces was isolated using standard protocols and 16S rRNA sequencing was performed using the Illumina MiSeq platform. For some studies, RAG1−/−mice were colonized (via gastric gavage) with 40 mg donor feces 1 week prior to adoptive transfer of naïve (CD4+CD45RBhigh) T-cells. Results Intestinal microbial populations are markedly different between the two institutions in healthy and colitic animals. Transplant of fecal microbiota from LSUHSC mice with chronic colitis into healthy RAG−/− recipients accelerates the onset, increases the incidence (>95%) and enhances the severity of chronic colitis following T cell transfer. However, colonization of healthy WT or RAG−/− mice (in the absence of T cell transfer) with colitic feces did not induce disease over the 8 week observation period. Conclusion We conclude that colonization of healthy RAG−/− mice with dysbiotic but nonpathogenic microbiota obtained from colitic mice markedly increases the incidence and severity of chronic colitis in the T cell transfer model.