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. 2024 Oct 31;187(22):6327-6345.e20.
doi: 10.1016/j.cell.2024.08.038. Epub 2024 Sep 24.

Microbial transformation of dietary xenobiotics shapes gut microbiome composition

Elizabeth J Culp  1 , Nora T Nelson  1 , Andrew A Verdegaal  1 , Andrew L Goodman  2
Affiliations

Microbial transformation of dietary xenobiotics shapes gut microbiome composition

Elizabeth J Culp et al. Cell. .

Abstract

Diet is a major determinant of gut microbiome composition, and variation in diet-microbiome interactions may contribute to variation in their health consequences. To mechanistically understand these relationships, here we map interactions between ∼150 small-molecule dietary xenobiotics and the gut microbiome, including the impacts of these compounds on community composition, the metabolic activities of human gut microbes on dietary xenobiotics, and interindividual variation in these traits. Microbial metabolism can toxify and detoxify these compounds, producing emergent interactions that explain community-specific remodeling by dietary xenobiotics. We identify the gene and enzyme responsible for detoxification of one such dietary xenobiotic, resveratrol, and demonstrate that this enzyme contributes to interindividual variation in community remodeling by resveratrol. Together, these results systematically map interactions between dietary xenobiotics and the gut microbiome and connect toxification and detoxification to interpersonal differences in microbiome response to diet.

Keywords: community composition; dietary xenobiotics; emergent interactions; gnotobiotics; microbial metabolism; microbiome.

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Conflict of interest statement

Declaration of interests A.L.G. serves on the scientific advisory boards of Seres Therapeutics, Taconic Biosciences, and Piton Therapeutics.

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