Discovery of new bioactive microbial metabolites in inflammatory bowel disease

Gut microbiota-associated bioactive compounds has been implicated as both disease-causing and –attenuating targets in GI disorder including inflammatory bowel diseases (IBD). However, discovery of new bioactive compounds relevant for IBD treatment has been severely limited, because most metabolite signals that are enriched or depleted in IBD patients’ fecal metabolome are uncharacterized. To address this challenge, we have computationally prioritized the metabolites putrescine from publicly-available IBD fecal metabolomic dataset and validated its biological function in vivo. We have also identified microbially-modified putrescine derivatives and these derivatives may selectively affect host colonic M2 macrophage cell populations in a gut microbiota-dependent manner. These finding suggest that the power of combined computational and experimental approaches for identifying microbially derived metabolites with general immunomodulatory activity and specific relevance for IBD patient care.