Personalized Mapping of Drug Metabolism by the Human Gut Microbiome.

TitlePersonalized Mapping of Drug Metabolism by the Human Gut Microbiome.
Publication TypeJournal Article
Year of Publication2020
AuthorsJavdan, B, Lopez, JG, Chankhamjon, P, Lee, Y-CJ, Hull, R, Wu, Q, Wang, X, Chatterjee, S, Donia, MS
Date Published2020 06 25
KeywordsAdult, Animals, Bacteria, Biomarkers, Pharmacological, Drug Evaluation, Preclinical, Feces, Female, Gastrointestinal Microbiome, Healthy Volunteers, Humans, Male, Metagenome, Metagenomics, Mice, Mice, Inbred C57BL, Microbiota, Pharmaceutical Preparations, Precision Medicine, RNA, Ribosomal, 16S

The human gut microbiome harbors hundreds of bacterial species with diverse biochemical capabilities. Dozens of drugs have been shown to be metabolized by single isolates from the gut microbiome, but the extent of this phenomenon is rarely explored in the context of microbial communities. Here, we develop a quantitative experimental framework for mapping the ability of the human gut microbiome to metabolize small molecule drugs: Microbiome-Derived Metabolism (MDM)-Screen. Included are a batch culturing system for sustained growth of subject-specific gut microbial communities, an ex vivo drug metabolism screen, and targeted and untargeted functional metagenomic screens to identify microbiome-encoded genes responsible for specific metabolic events. Our framework identifies novel drug-microbiome interactions that vary between individuals and demonstrates how the gut microbiome might be used in drug development and personalized medicine.

Alternate JournalCell
PubMed ID32526207
PubMed Central IDPMC8591631
Grant ListDP2 AI124441 / AI / NIAID NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States