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Immune recognition of microbial metabolites

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.

Key advances

  • 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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Fig. 1: Interactions between microbial metabolites and immune cells.


  1. 1.

    Chun, E. et al. Metabolite-sensing receptor Ffar2 regulates colonic group 3 innate lymphoid cells and gut immunity. Immunity (2019).

    Article  PubMed  Google Scholar 

  2. 2.

    Bachem, A. et al. Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8+ T cells. Immunity 51, 285–297 (2019).

    CAS  Article  Google Scholar 

  3. 3.

    Schulthess, J. et al. The short chain fatty acid butyrate imprints an antimicrobial program in macrophages. Immunity 50, 432–445 (2019).

    CAS  Article  Google Scholar 

  4. 4.

    Skelly, A. N. et al. Mining the microbiota for microbial and metabolite-based immunotherapies. Nat. Rev. Immunol. 19, 305–323 (2019).

    CAS  Article  Google Scholar 

  5. 5.

    Morita, N. et al. GPR31-dependent dendrite protrusion of intestinal CX3CR1+ cells by bacterial metabolites. Nature 566, 110–114 (2019).

    CAS  Article  Google Scholar 

  6. 6.

    Colosimo, D. A. et al. Mapping interactions of microbial metabolites with human G-protein-coupled receptors. Cell Host Microbe 26, 273–282.e7 (2019).

    CAS  Article  Google Scholar 

  7. 7.

    Chen, H. et al. A forward chemical genetic screen reveals gut microbiota metabolites that modulate host physiology. Cell 177, 1217–1231 (2019).

    CAS  Article  Google Scholar 

  8. 8.

    Constantinides, M. G. et al. MAIT cells are imprinted by the microbiota in early life and promote tissue repair. Science 366, eaax6624 (2019).

    CAS  Article  Google Scholar 

  9. 9.

    Legoux, F. et al. Microbial metabolites control the thymic development of mucosal-associated invariant T cells. Science 366, 494–499 (2019).

    CAS  Article  Google Scholar 

  10. 10.

    Godfrey, D. I. et al. The biology and functional importance of MAIT cells. Nat. Immunol. 20, 1110–1128 (2019).

    CAS  Article  Google Scholar 

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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).

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Correspondence to Wendy S. Garrett.

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The author is a member of the scientific advisory boards of Kintai Therapeutics, Leap Therapeutics, Evelo Biosciences and Tenza.

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Garrett, W.S. Immune recognition of microbial metabolites. Nat Rev Immunol 20, 91–92 (2020).

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