Discovery of therapeutic microbial metabolites in Inflammatory Bowel Diseases.

The bacteria in the human colon can influence gastrointestinal lining cells [intestinal epithelial cells (IECs)] and immune cells within the intestines and throughout the body. One way that bacteria do this is through their metabolites, the chemicals they produce. By influencing IECs and immune cells, gut bacterial metabolites affect resistance and susceptibility to Inflammatory Bowel Disease (IBD), as bacterial metabolites can positively or negatively affect intestinal inflammation and IEC function. Using the methods employed in most human IBD metabolite stool studies, 99% of bacterial metabolites remain unidentified. We have developed a workflow to determine which of these molecules are potentially important for IBD, which are bacterially derived, and which are active or act on immune cells and IECs. In this proposal, we will focus on determining the activity of a class of bacterial molecules called fatty acid amides. We will investigate if they change the activity of IECs and an important immune cell type called dendritic cells. A subset of the fatty acid amide compounds that we find act on IECs and/or dendritic cells will be tested in two models of colonic injury and inflammation.