Grant: Project Grant

Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic recurring inflammatory diseases of the gut. Intestinal scarring or fibrosis, which is usually the consequence of chronic inflammation, is a common complication of IBD mainly in CD. In recent years progress has been made in developing better treatment in IBD. However, disadvantages with current treatment strategies persist as the drugs used for the treatment may cause many serious side effects, and many patients do not respond well to these treatments. In addition, current therapies do not prevent, nor they reverse established scarring or fibrosis in IBD. These demerits suggest the need for the development of better treatment strategies in IBD identifying new targets that halt IBD progression. Tryptophan is an essential amino acid supplied by dietary proteins. 5-methoxytryptophan (5-MTP) is a tryptophan metabolite (biological by-product). Recent studies have demonstrated the anti-inflammatory and anti-fibrotic effects of 5-MTP in various organs including kidney, lungs, and liver. Preliminary studies in our laboratory have shown that treatment with 5-MTP significantly reduces the severity of colitis and scarring/fibrosis. We are now planning to further explore the roles of 5-MTP in regulation of gut barrier function, inflammation, microbiota, and fibrosis using mouse models and mini-organs grown in a culture dish. In addition to providing new information on the role of 5-MTP in inflammation and fibrosis in the gut this research may ultimately help in developing novel treatment strategy for taking better care of patients with gut inflammatory disorders including IBD.