This project involves both human-based studies, human derived intestinal organoids, and animal models. The project is based on the principle that complex immune disorders like IBD are triggered by environmental, dietary, and microbial factors on a background of host genetic susceptibility. The studies involve deep investigations of the gut microbiome and host immune and inflammatory pathways.

1. To define specific pathobionts and their mechanisms of action that trigger host (human) immune and inflammatory pathways

2. Examine host mechanisms that render human subjects at risk for IBD.

Two human IBD models will be studied. The first involved ulcerative colitis patients who have undergone total removal of the colon (colectomy) with ileal pouch anal anastomosis (creation of a pseudorectum). Half of these patients will develop an inflammatory disease of the ileal pouch called "pouchitis" within two years of the procedure, which has hallmarks of the original disease. Non-IBD patients who undergo the same procedure rarely develop this complication, suggesting that some of the original pathophysiological events are recapitulated. These patients are being followed prospectively over two years and endoscopic samples of both the pouch microbiome and mucosa are being obtained. Students would be involved in studying specific microbes that might be triggering the disease or defining mechanisms on the patient side that render them susceptible to disease. The second project involves studies of Crohn's disease (CD) that involves the terminal ileum. Here, the role of a novel innate immune molecule made by Paneth cells of the gut mucosa will be studied to determine if its dysfunction or loss of function in CD is an important aspect of disease pathogenesis.

All software for data analysis will be provided by Dr. Chang's lab.

Weekly lab meetings, GI research conferences, and monthly meetings of the Microbiome Medicine program.