Metabolomics

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Mapping human microbiome drug metabolism by gut bacteria and their genes


ABSTRACT:

Individuals vary widely in their drug responses, which can be dangerous and expensive due to treatment delays and adverse effects. Growing evidence implicates the gut microbiome in this variability, however the molecular mechanisms remain largely unknown. We measured the ability of 76 diverse human gut bacteria to metabolize 271 oral drugs and found that many of these drugs are chemically modified by microbes. We combined high-throughput genetics with mass spectrometry to systematically identify drug-metabolizing microbial gene products. These microbiome-encoded enzymes can directly and significantly impact intestinal and systemic drug metabolism in mice, and can explain drug-metabolizing activities of human gut bacteria and communities based on their genomic contents. These causal links between microbiota gene content and metabolic activities connect interpersonal microbiome variability to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications.

Additional data related to this study can also be found by the following links;
- Raw sequencing data; ENA (accession no. PRJEB31790)
- Data for Figures; FigShare 
- Analysis pipleine schemes, scripts and input files for analzing data and generating figures; GitHub and archived Zenodo

INSTRUMENT(S): Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Michael Zimmermann  

PROVIDER: MTBLS896 | MetaboLights | 2019-07-10

REPOSITORIES: MetaboLights

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Publications

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

Zimmermann Michael M   Zimmermann-Kogadeeva Maria M   Wegmann Rebekka R   Goodman Andrew L AL  

Nature 20190603 7762


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  ...[more]

Publication: 1/3

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