Presented by: Wei Li
Primary bile acids discharged into the gut lumen are subject to biotransformation by commensal bacteria and converted into secondary metabolites. These bile acids and bile acid metabolites are signaling molecules that regulate immune homeostasis, including the differentiation of CD4+ T cells into distinct T cell subsets. Previously, we have shown that the bile acid metabolite isoallolithocholic acid (isoalloLCA) enhances the differentiation of anti-inflammatory regulatory T cells (Treg cells). Here, we identify gut bacteria that synthesize isoalloLCA from 3-oxolithocholic acid and uncover a gene cluster responsible for the conversion in members of the abundant human gut bacterial phylum Bacteroidetes. Moreover, the levels of isoalloLCA and its biosynthetic genes are significantly reduced in patients with inflammatory bowel diseases, suggesting that isoalloLCA and its bacterial producers may play a critical role in maintaining immune homeostasis in humans. Our results reveal new ways in which commensal bacteria regulate immune tolerance in the gut, laying the groundwork for potential new therapeutic avenues to control IBD.