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MICROBIOME

Gut bugs disrupt cancer drugs

Nature Reviews Microbiology volume 20, page 704 (2022)Cite this article

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The gut microbiome can alter the metabolism of anti-cancer drugs, potentially affecting their safety and efficacy, although the mechanisms are poorly understood. Now, Spanogiannopoulos et al. show that the efficacy of fluoropyrimidine chemotherapeutics is reduced by an enzyme expressed by gut microbiota.

In mammalian cells, the metabolism of fluoropyrimidines into inactive metabolites is controlled by dihydropyrimidine dehydrogenase. E. coli possess an orthologous protein that is encoded by two genes — preT and preA — found within the preTA operon. Asking whether these genes are necessary for the inactivation of fluoropyrimidines, the authors knocked out the preTA operon in E. coli and found that its loss entirely prevented drug inactivation. This effect could be fully rescued by the re-introduction of preTA, indicating that the preT and preA genes are necessary and sufficient for the inactivation of fluoropyrimidine by E. coli in vitro.

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  • Lindell, A. E., Zimmermann-Kogadeeva, M. & Patil, K. R. Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota. Nat. Rev. Microbiol. 20, 431–443 (2022)

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  1. Nature Reviews Microbiology http://www.nature.com/nrmicro/

    Michael Attwaters

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  1. Michael Attwaters
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Correspondence to Michael Attwaters.

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Attwaters, M. Gut bugs disrupt cancer drugs. Nat Rev Microbiol 20, 704 (2022). https://doi.org/10.1038/s41579-022-00812-y

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