Bacterial proteolytic function in inflammatory bowel disease
Differences in the composition of bacteria within the gut have been found in patients with inflammatory bowel disease (IBD) and healthy people. In addition to this, bacterial functional differences may also contribute to inflammation in IBD, but it is difficult to determine whether these changes are cause or the consequence of disease. Proteases, which are enzymes that break down proteins, are produced by bacteria in the gut. Proteases can be inflammatory, and it has been shown that patients with IBD have higher activity of proteases in stool, but whether this activity comes from bacteria is not known. We will investigate whether proteases are increased before the onset of IBD, whether this bacteria contribute to this, and whether they cause inflammation in animal models of colitis. Finally, we will determine whether we can inhibit bacterial proteases using specific probiotics to reduce inflammation. To address these objectives, we will use fecal samples collected from a unique cohort of patients: 1) subjects who are at healthy, but at risk for IBD, and who go on to develop IBD later; 2) these same patients at IBD diagnosis; 3) subjects who are at risk for IBD, but have remained healthy (controls).