Compositional changes to the ileal microbiome precede the onset of spontaneous ileitis in SHIP deficient mice

Abstract

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 and specific commensal populations 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. Finally, antibiotic treatment reduced the development of intestinal inflammation in SHIP−/− mice. 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.

Temporal and region-specific effects of sleep fragmentation on gut microbiota and intestinal morphology in Sprague Dawley rats

“…It is well known that each gut location is anatomically and functionally diverse; and previous metagenomic studies have demonstrated that microbiota composition and intestinal barrier function are dependent on location. [36][37][38] Yet, most studies of sleep disturbances have focused on microbial characterization of the colonic or fecal communities alone. [19][20][21][22][39][40][41] While previous experiments by our laboratory have shown that colonic and fecal community profiles in SPF Sprague Dawley rats are similar (Supplemental Figure 6), our regionally distinctive microbiota data emphasizes the importance of assessing microbiota changes throughout the gut.…”

Intermittent cafeteria diet identifies fecal microbiome changes as a predictor of spatial recognition memory impairment in female rats

“…Coprobacter_OTU66 was putatively identified as M. intestinale strain YL27 and has only been recently sequenced 61 . In mice, this strain has been associated with a healthy phenotype 62 and low-fat diet consumption 61 . Future studies manipulating this strain in rats may provide further insight into its role in diet-induced obesity and cognitive dysfunction.…”

Links Between Inflammatory Bowel Disease and Chronic Obstructive Pulmonary Disease

“…While these data suggest that inflammation is sufficient to induce dysbiosis, it is also clear that genetic susceptibility plays a role since T. gondii induced heightened dysbiosis and AIEC invasion in mice lacking the ileitis susceptibility gene NOD2, while disease was significantly muted in mice lacking the proinflammatory C-C chemokine receptor 2 (CCR2), which are a model of ileitis resistance (58). Furthermore, it has been demonstrated in an alternative genetic knock out model of ileitis susceptibility that dysbiosis precedes the onset of ileitis (59).…”