2050: Defining the Genetic Susceptibility to Granulomatous Colitis, a Severe Form of Inflammatory Bowel Disease
Grant Status: Open
Granulomatous colitis is a severe inflammatory bowel disease (IBD), usually diagnosed in young dogs. Affected dogs present with hemorrhagic diarrhea, often progressing to weight loss and debilitation. Recent studies have identified invasive Escherichia coli (E. coli) bacteria within macrophages in the inflamed large intestine, and eradication of E.coli induces dramatic clinical and histologic improvement. Unfortunately, the emergence of antimicrobial resistance has greatly reduced our ability to treat this disease, and persistently affected dogs are frequently euthanized. The type of E.coli isolated from dogs with granulomatous colitis is very similar to adherent and invasive E. coli (AIEC) associated with IBD in people. This type of E.coli are considered opportunistic pathogens that can exploit genetic defects in bacterial killing in an IBD susceptible individual. Dr. Simpson suspects this is due to a heritable abnormality that confers susceptibility to invasion and persistence of E.coli. In preliminary studies his research group has identified a region of the canine genome that is associated with granulomatous colitis affected dogs. This region contains candidate genes associated with IBD in people and mouse models, and has been specifically linked to sensing and killing of E.coli. The purpose of this study is to identify the gene(s), causal variant(s) and cellular pathways involved in the development of granulomatous colitis. This would enable the development of screening tests to eradicate this disease, and advance understanding of the development of IBD in dogs and people.
None at this time.
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