Cross-talk between gut bacteria and intestinal epithelial cells in IBD

Description: The human colon is home to more than 100 trillion bacteria, which normally provide helpful functions such as regulating digestion and stimulating the immune system. For the colon to function properly, it is important to maintain the right balance of bacteria. Some types of bacteria are beneficial, while others can cause inflammation. One of the key questions in IBD is why the mix of bacteria in the colon becomes unbalanced. This may be due to a combination of genetiC, dietary and environmental factors. One potential strategy to restore balance in IBD patients is therapy with "pro biotic" bacteria, such as those found in yogurt and dietary supplements. One of the ways that the immune system maintains the right mix of bacteria in the colon is by making antibodies that promote the growth of benefICial bacteria and kill disease-causing bacteria. Antibodies are produced by white blood cells, and are transported into the colon by a specialized protein called the "polymeric immunoglobulin receptor", or "plgR" for short. Recent research in our laboratory has shown that patients with Crohn's Disease (CD) and ulcerative colitis (UC) are defective in their production of pIgR protein, thus slowing down the process of antibody transport into the colon. Part of the reason for this defect may be unbalanced mix of bacteria in the colon of IBD patients. Our research has shown that probiotic bacteria stimulate the colon to produce more plgR protein, which may speed up the transport of antibodies into the colon and help to restore the balanced mix of bacteria. Our proposed research is designed to answer three questions: (1) What types of probiotlc bacteria are most effective in stimulating the production of plgR protein in the colon? (2) How do pro biotic bacteria interact with the cells lining the intestine (epithelial cells and white blood cells) to cause them to produce more plgR protein? (3) Does stimulation of plgR protein by pro biotic bacteria reduce intestinal Inflammation? To address these questions, we will use two different experimental strategies. In the first strategy, we will mix different kinds of pro biotic bacteria with human epithelial cells and white blood cells in Petri dishes, and measure the production of plgR protein. We will compare the responses of cells from CD patients, UC patients, and normal volunteers. In the second strategy, we will study intestinal inflammation in normal mice compared to mice with genetic defects in the production of pIgR protein. The mice will be treated with different kinds of probiotic bacteria to see if this therapy can restore normal production of pIgR protein and reduce intestinal inflammation.