Mapping human microbiome drug metabolism by gut bacteria and their genes

By Michael Zimmermann, M. Zimmermann-Kogadeeva, R. Wegmann, A. Goodman. Nature, 2019

972 citations recorded by the source corpus.

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. High-throughput genetic analyses combined with mass spectrometry reveal that the gene products of diverse human gut bacteria affect a wide range of oral drugs, as well as drug metabolism in mice.

Subfields: Food Science, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/cf4d3f87dde4b3a663ab4ba934dcb47ca274b32e

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In Food Science

Alla L. Lapidus

In Molecular Biology

Citations in the corpus

Gut Microbiome: Profound Implications for Diet and Disease (2019, background): “Enzymes in gut bacteria across the main taxonomic groupings have been shown to metabolize 176 common oral drugs, suggesting that differences in gut microbiota may shape individual responses to drug therapy [324].”
MGnify: the microbiome analysis resource in 2020 (2019, background): “…sludge performance (8); have highlighted differences in the gut microbiota of babies delivered by caesarean-section compared to vaginal birth (9); and have discovered a number of microbial gene products that metabolize orally administered drugs, with potential effects upon medical therapy (10).”