Grant Abstract: Microbiota-immune interactions that promote intestinal homeostasis

Grant Number: 5R01AT011423-02
PI Name: Round
Project Title: Microbiota-immune interactions that promote intestinal homeostasis

Abstract: Individuals with inflammatory bowel disease (IBD) are more likely to develop metabolic abnormalities, such as diabetes, however little is known about the basis of this connection. Multiple studies have now shown that changes to the composition of the microbiota are a factor in multiple diseases, including IBD and diabetes. Moreover, the studies that have examined the composition of the microbiota within individuals with IBD or diabetes, have identified similar changes to these resident communities. We have recently identified a mouse model that develops worsened colitis and spontaneous obesity and insulin resistance. Both of these diseases are reliant on the microbiota and can be rescued by a microbiota transplant, or an oral gavage of a purified population of Clostridia. Thus, we hypothesize that the growing incidence of IBD and diabetes may be attributable to similar defects in the microbiota and might explain the why some individuals are more prone to develop both diseases. Based on this, we propose a series of experiments to identify a defined consortia of Clostridia that will function to prevent disease and explore the common mechanisms, including effects of the immune system, between IBD and metabolism that might lead to the development of these diseases. Thus, our findings will be among the first to identify a consortia of bacteria that could be used for therapeutic intervention/prevention of IBD and/or diabetes and allow for an in-depth mechanistic understanding of how these protective bacteria maintain intestinal homeostasis. PUBLIC HEALTH RELEVANCE: Extra-intestinal manifestations, including insulin resistance, lipid abnormalities and diabetes can occur in 25- 40% of IBD patients, suggesting a link between metabolic defects and chronic intestinal inflammation. Here will test a role for a specific subset of commensal bacteria that might underlie the connection between these diseases.

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