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Host–microbiome orchestration of the sulfated metabolome

Nature Chemical Biology volume 20, pages 410–421 (2024)Cite this article

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Abstract

Recent studies have demonstrated that metabolites produced by commensal bacteria causally influence health and disease. The sulfated metabolome is one class of molecules that has recently come to the forefront due to efforts to understand the role of these metabolites in host–microbiome interactions. Sulfated compounds have canonically been classified as waste products; however, studies have revealed a variety of physiological roles for these metabolites, including effects on host metabolism, immune response and neurological function. Moreover, recent research has revealed that commensal bacteria either chemically modify or synthesize a variety of sulfated compounds. In this Review, we explore how host–microbiome collaborative metabolism transforms the sulfated metabolome. We describe bacterial and mammalian enzymes that sulfonate and desulfate biologically relevant carbohydrates, amino acid derivatives and cholesterol-derived metabolites. We then discuss outstanding questions and future directions in the field, including potential roles of sulfated metabolites in disease detection, prevention and treatment. We hope that this Review inspires future research into sulfated compounds and their effects on physiology.

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Fig. 1: The host and the microbiome produce sulfated metabolites through collaborative metabolism.
Fig. 2: Microbial desulfation of sulfated carbohydrates influences host biology.
Fig. 3: Amino acid-derived sulfated metabolites exhibit diverse biological effects.
Fig. 4: Host and microbial enzymes biosynthesize cholesterol-derived sulfated metabolites.
Fig. 5: Cholesterol-derived sulfated metabolites are associated with host phenotypes.

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Acknowledgements

This work was supported by National Institutes of Health grants R35 GM128618, R01 DK126855 and R01 DK110559 and an Alfred P. Sloan Fellowship (A.S.D.). S.N.C. acknowledges an American Heart Association Postdoctoral Fellowship and a National Institutes of Health K99/R00 Pathway to Independence Award (K99 DK128503). We thank M. Tran for helpful discussions, and we acknowledge BioRender for help with figure creation. Correspondence should be addressed to S.N.C. and A.S.D.

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  1. These authors contributed equally: Gabriel D. D’Agostino, Snehal N. Chaudhari.

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  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA

    Gabriel D. D’Agostino, Snehal N. Chaudhari & A. Sloan Devlin

  2. Department of Biochemistry, University of Wisconsin, Madison, WI, USA

    Snehal N. Chaudhari

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G.D.D’A., S.N.C. and A.S.D. contributed to discussions and wrote the manuscript.

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Correspondence to Snehal N. Chaudhari or A. Sloan Devlin.

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A.S.D. is an ad hoc consultant for Takeda Pharmaceuticals, Axial Therapeutics and Ferring Pharmaceuticals. S.N.C. is an ad hoc consultant for Metis Therapeutics. G.D.D’A. declares no competing interests.

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D’Agostino, G.D., Chaudhari, S.N. & Devlin, A.S. Host–microbiome orchestration of the sulfated metabolome. Nat Chem Biol 20, 410–421 (2024). https://doi.org/10.1038/s41589-023-01526-9

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