Mapping human microbiome drug metabolism by gut bacteria and their genes
Open accessAbstract
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.
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The microbiome is a general mediator of xenobiotic metabolism, capable of activating, inactivating or recycling numerous drugs.
“the microbiome is a general mediator of xenobiotic metabolism, capable of activating, inactivating or recycling numerous drugs [103,104,105].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [103]
The Abstract gives examples of gut microbes activating and inactivating drugs, and the Discussion reports that about two thirds of the 271 assayed drugs were metabolized by at least one bacterial strain. Those passages support broad drug-metabolizing capacity, but the passages found do not establish that the microbiome recycles drugs. Page numbers were not provided in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe mouth is the first microbial compartment that a swallowed supplement meets, and oral bacteria carry reductive and hydrolytic activities of the same type that make the intestinal microbiota a determinant of drug disposition.
“The mouth is the first microbial compartment that a swallowed supplement meets, and oral bacteria carry reductive and hydrolytic activities of the same type that make the intestinal microbiota a determinant of drug disposition [103,104,105].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [103]
The Abstract and Discussion describe gut bacteria metabolizing oral drugs and potentially affecting intestinal and systemic drug exposure. The section on identifying drug-metabolizing gut bacteria discusses hydrolysis and reduction, but the cited passages do not establish that the mouth is the first microbial compartment a swallowed supplement meets or that oral bacteria have those activities. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe oral compartment, where berberine reaches its highest concentrations of all, is unexamined and belongs in the same research program.
“The oral compartment, where berberine reaches its highest concentrations of all, is unexamined and belongs in the same program [103,104,105,106,107,108].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [103]
The ‘Identification of drug-metabolizing bacteria from the human gut microbiome’ section describes a program of testing drug metabolism by gut bacteria, and the Methods describe fecal sampling; this study does not examine the oral compartment. The paper does not establish that berberine reaches its highest concentrations there or that the oral compartment is unexamined more generally (searched: berberine, oral microbiome, saliva). No page numbers were available in our copy. (LLM, conf=0.81)
Experimental — accuracy not yet measuredThe gut microbiome has a profound impact on drug metabolism, inter-individual drug responsiveness, and drug efficacy with time.
“The gut microbiome has a profound impact on drug metabolism, inter-individual drug responsiveness, and drug efficacy with time [154].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [154]
The Abstract reports extensive microbial drug metabolism and says growing evidence implicates the gut microbiome in variation in drug responses. The Discussion says microbiome metabolism could affect drug exposure, but the paper does not establish that the microbiome changes clinical drug efficacy over time. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNo study has yet measured the disposition of a co-administered drug before and after berberine while characterizing the microbiota in the same subjects, which is what would move Axis 4 from candidate to demonstrated.
“No study has yet measured the disposition of a co-administered drug before and after berberine while characterizing the microbiota in the same subjects, which is what would move Axis 4 from candidate to demonstrated.”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [103]
The Extended Data describe drug-metabolism assays using bacterial strains and donated gut communities, not before-and-after drug-disposition measurements in people. Searches for berberine and for a same-subject pharmacokinetic study found no passage establishing the claimed absence of such studies or the proposed threshold for demonstrating Axis 4. No page numbers are available in our copy. (LLM, conf=0.75)
Experimental — accuracy not yet measured
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Self-citation
- Authors
- Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R., & Goodman, A. L.
- Affiliations
- Yale University (US)
- Corresponding author
- Goodman, Andrew L.
- Venue
- Nature
- Published
- 2019-06-03
- Volume
- 570
- Issue
- 7762
- Pages
- 462-467
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6597290
- OpenAlex
- W2948160364
- Cited by
- 1,160
- References
- 40
- Citations by year
- 2026: 169 · 2025: 172 · 2024: 167 · 2023: 147 · 2022: 162 · 2021: 173 · 2020: 131 · 2019: 38 · 2018: 1
- FWCI
- 127.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Crohn's and Colitis Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (178482, 162256, 177915)
- National Institutes of Health (UL1TR001863)
- National Institute of General Medical Sciences (DP2GM105456, R35GM118159)
- National Institute of Allergy and Infectious Diseases (U01AI124275)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK114793)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- gut microbiota, drug metabolism, human gut bacteria, microbial enzymes, interindividual variability, intestinal drug metabolism, personalized medicine
- MeSH terms
- Gastrointestinal Microbiome, Bacteroides thetaiotaomicron, Animals, Bacteria, Diltiazem, Pharmaceutical Preparations, Female, Germ-Free Life, Humans, Male, Substrate Specificity, Genome, Bacterial, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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