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Nature. 2019 Jun;570(7762):462-467. doi: 10.1038/s41586-019-1291-3. Epub 2019 Jun 3.

Mapping human microbiome drug metabolism by gut bacteria and their genes.

Author information

1
Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University School of Medicine, New Haven, CT, USA.
2
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
3
Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University School of Medicine, New Haven, CT, USA. andrew.goodman@yale.edu.

Abstract

Individuals vary widely in their responses to medicinal drugs, which can be dangerous and expensive owing to treatment delays and adverse effects. Although increasing evidence implicates the gut microbiome in this variability, the molecular mechanisms involved remain largely unknown. Here we show, by measuring the ability of 76 human gut bacteria from diverse clades to metabolize 271 orally administered drugs, that many drugs are chemically modified by microorganisms. We combined high-throughput genetic analyses with mass spectrometry to systematically identify microbial gene products that metabolize drugs. These microbiome-encoded enzymes can directly and substantially affect intestinal and systemic drug metabolism in mice, and can explain the drug-metabolizing activities of human gut bacteria and communities on the basis of their genomic contents. These causal links between the gene content and metabolic activities of the microbiota connect interpersonal variability in microbiomes to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications.

PMID:
31158845
PMCID:
PMC6597290
[Available on 2019-12-03]
DOI:
10.1038/s41586-019-1291-3

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