Microbial Ecology of Helicobacter-induced Colitis

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Inflammatory bowel disease (IBD) is characterized by the[unreadable] development of an abnormal inflammatory response in the gastrointestinal tract. The[unreadable] microbiota of the intestinal tract, in part via interactions with the host epithelium and[unreadable] immune system are thought to drive this proinflammatory state. The gut microbiota[unreadable] represents a complex community of bacteria that until recently has only been partly[unreadable] characterized. The use of culture-independent techniques to examine complex microbial[unreadable] communities has started to reveal details about the structure and composition of the gut[unreadable] microbiota. To date, minimal work has been done to define differences in the structure of[unreadable] the mucosa-associated microbiota of the intestinal tract secondary to alterations in the[unreadable] host immune system, the presence of pathogens, antibiotic treatment or the presence of[unreadable] beneficial (probiotic) organisms. In this proposal, an existing collaboration between[unreadable] scientists with interests in microbial ecology and infectious diseases/bacterial[unreadable] pathogenesis plan to investigate the role of the intestinal microbiota in IBD utilizing a well[unreadable] developed murine model of IBD in IL-10-/- mice triggered by the presence of the[unreadable] bacterium Helicobacter hepaticus.[unreadable] [unreadable] Specifically we propose to 1) determine the influence of the host immune system[unreadable] on shaping the community structure of the mucosa-associated intestinal microbiota 2)[unreadable] determine how H. hepaticus infection and the development of colitis changes the[unreadable] mucosa-associated intestinal microbiota and 3) determine if antibiotics can modify the[unreadable] development of IBD in H. hepaticus-infected IL-10-/- animals. The proposed experiments[unreadable] will provide insight into the mechanism by which infectious agents can trigger shifts in[unreadable] the indigenous microbiota that lead to aberrant host responses and disease states. This[unreadable] information will directly impact patients with inflammatory bowel disease, leading to a[unreadable] greater understanding of the underlying disease mechanisms and the development of[unreadable] novel treatment modalities.[unreadable] [unreadable] Relevance: Inflammatory bowel disease in humans is thought to arise from an abnormal[unreadable] interaction between the immune system and the microbes that normally inhabit the gut.[unreadable] This project intends to define abnormalities in the community of gut microbes that[unreadable] predispose to the development of inflammatory bowel disease, pointing the way towards[unreadable] new therapies for this chronic disease that affects 1 in 1000 people in developed[unreadable] countries.