Compositional changes to the ileal microbiome precede the onset of spontaneous ileitis in SHIP deficient mice
Autor: | Jean Philippe Sauve, Peter Allan Dobranowski, Chris Tang, Susan C. Menzies, Laura M. Sly |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Microbiology (medical) Crohn’s disease ileitis microbiome Disease Biology Microbiology 03 medical and health sciences Feces Mice 0302 clinical medicine Crohn Disease Ileum RNA Ribosomal 16S intestinal inflammation medicine Deficient mouse Animals Ileitis Microbiome Cecum Mice Knockout Crohn's disease Bacteria fungi Gastroenterology Gastrointestinal inflammation medicine.disease Ulcerative colitis digestive system diseases Gastrointestinal Microbiome Mice Inbred C57BL Disease Models Animal 030104 developmental biology Infectious Diseases Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases Immunology Research Paper/Report Etiology 030211 gastroenterology & hepatology SHIP |
Zdroj: | Gut Microbes |
ISSN: | 1949-0984 |
Popis: | 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. |
Databáze: | OpenAIRE |
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