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SHIP-microbiome interactions in intestinal inflammation

University of British Columbia

Inflammatory bowel disease, encompassing both ulcerative colitis and Crohn’s disease, is characterized by chronic, relapsing-remitting gastrointestinal inflammation of unknown etiology. SHIP deficient mice develop fully penetrant, spontaneous ileitis at 6 weeks of age, and thus offer a tractable model of Crohn’s disease-like inflammation. Since disruptions to the microbiome are implicated in the pathogenesis of Crohn’s disease, we conducted a 16S rRNA gene survey of the ileum, cecum, colon, and stool contents of SHIP+/+ and SHIP-/- mice. We predicted that diversity and compositional changes would occur after, and possibly prior to, the onset of overt disease. No differences were found in alpha diversity, but significant changes in beta diversity, specific commensal populations, and the inferred metagenome were observed in the ileal compartment of SHIP deficient mice after the onset of overt disease. Specifically, reductions in the Bacteroidales taxa, Muribaculum intestinale, and an expansion in Lactobacillus were most notable. In contrast, expansions to bacterial taxa previously associated with inflammation, including Bacteroides, Parabacteroides, and Prevotella were observed in the ilea of SHIP deficient mice prior to the onset of overt disease. Thus, our findings indicate that SHIP is involved in maintaining ileal microbial homeostasis. These results have broader implications for humans, since reduced SHIP protein levels have been reported in people with Crohn’s disease.

Text

2019-10-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/67401

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/