LAUSR

Mucosal immunology research continues its fascination with microbial metabolites. In 2019, researchers uncovered extended functions for microbial metabolites in immunity, deepening our understanding of the regulation and function of metabolite-reactive immune cells, and revealed the receptors by which immune cells can recognize bioactive microbial metabolites. In the past year, researchers have gained a deeper understanding of the interactions between immune cells and microbially derived metabolites. Wendy Garrett describes the new insights into the receptors, immune cells and pathways triggered by microbial metabolites. Short-chain fatty acids affect host defence by acting on group 3 innate lymphoid cells via free fatty acid receptor 2 (FFAR2), on macrophages through metabolic reprogramming and on memory CD8 + T cells through an FFAR2-dependent and FFAR3-dependent shift in T cell metabolism. Screens have revealed microbial metabolites that activate G protein-coupled receptors (GPCRs) affecting numerous host physiological processes. Mucosal-associated invariant T (MAIT) cells rely on early life bacterial exposures for their development, and skin-resident MAIT cells play crucial roles in tissue repair. Effective mining of public resources of microbial metabolites, GPCR–metabolite interactions and immune cell transcriptomes is accelerating the pace of discovery and translation of immune–microbial metabolite interactions for promoting health and mitigating disease.