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.
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.
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The author thanks members of the Garrett laboratory for stimulating discussions. Work related to this piece is supported by the US National Institutes of Health (R01CA154426 and R24DK11049).
The author is a member of the scientific advisory boards of Kintai Therapeutics, Leap Therapeutics, Evelo Biosciences and Tenza.
Human Microbiome Bioactives Resource (HMBR): https://www.microbiome-bioactives.org/
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Garrett, W.S. Immune recognition of microbial metabolites. Nat Rev Immunol 20, 91–92 (2020). https://doi.org/10.1038/s41577-019-0252-2