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Identifying microbiome contributions to xenobiotic metabolism and toxicity

16.12.2021 12:30 pm Joint Microbiological Colloquium Michael Zimmermann

Speaker: Michael Zimmermann (EMBL)

Host: Hannes Link (IMIT)

Ort: Hybridevent

  • Hörsaal N2
    Hörsaalzentrum Morgenstelle
    Auf der Morgenstelle 16
    72076 Tübingen

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  • Online via Zoom

 

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lisa.bleul@med.uni-tuebingen.de


Abstract:

Individuals vary widely in their drug responses, which can be dangerous and expensive due to significant treatment delays and adverse effects. Growing evidence implicates the gut microbiome in this variability, however the molecular mechanisms remain mostly unknown. To systematically map the drug metabolizing capacity of the gut microbiota and to assess its potential contribution to drug metabolism, we measured the ability of 76 diverse human gut bacteria to metabolize each of 271 oral drugs. We found that two thirds of these drugs are chemically modified by at least one of the tested microbes. Through combination of high-throughput bacterial genetics with mass spectrometry, we systematically identified drug-metabolizing microbial enzymes. Further, we developed experimental and computational approaches to separate host and gut microbiota contributions to drug metabolism in vivo. These allowed us to quantify and predict microbiota contributions to drug metabolism and toxicity. These causal links between microbiota gene content and metabolic activities connect inter-individual microbiome variability to interpersonal differences in the metabolism of drugs and other xenobiotics.