Cited by 656Pharmacogenetics and Drug MetabolismGut microbiota and healthDrug Transport and Resistance Mechanisms

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Gut microbiome interactions with drug metabolism, efficacy, and toxicity

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Wilson, Ian D., Nicholson, Jeremy K.·2017·Translational Research

DOI 10.1016/j.trsl.2016.08.002PMC PMC5718288

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Abstract

The gut microbiota has both direct and indirect effects on drug and xenobiotic metabolisms, and this can have consequences for both efficacy and toxicity. Indeed, microbiome-driven drug metabolism is essential for the activation of certain prodrugs, for example, azo drugs such as prontosil and neoprontosil resulting in the release of sulfanilamide. In addition to providing a major source of reductive metabolizing capability, the gut microbiota provides a suite of additional reactions including acetylation, deacylation, decarboxylation, dehydroxylation, demethylation, dehalogenation, and importantly, in the context of certain types of drug-related toxicity, conjugates hydrolysis reactions. In addition to direct effects, the gut microbiota can affect drug metabolism and toxicity indirectly via, for example, the modulation of host drug metabolism and disposition and competition of bacterial-derived metabolites for xenobiotic metabolism pathways. Also, of course, the therapeutic drugs themselves can have effects, both intended and unwanted, which can impact the health and composition of the gut microbiota with unforeseen consequences.

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Authors: Wilson, I. D., & Nicholson, J. K.
Affiliations: Imperial College London (GB)
Corresponding author: Wilson, Ian D.
ORCID: Wilson, Ian D.
Nicholson, Jeremy K.
Venue: Translational Research
Publisher: Elsevier BV
Published: 2017-01
Volume: 179
Pages: 204-222
ISSN: 1878-1810 (ISSN-L)
1931-5244
DOI: 10.1016/j.trsl.2016.08.002
PMC: PMC5718288
OpenAlex: W2517182458
Cited by: 656
References: 141
Citations by year: 2026: 81 · 2025: 74 · 2024: 66 · 2023: 71 · 2022: 70 · 2021: 91 · 2020: 75 · 2019: 63 · 2018: 42 · 2017: 20
FWCI: 7.48
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Translational research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
Funders: Wellcome Trust (104933)
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, xenobiotic metabolism, drug efficacy, drug toxicity, prodrug activation, sulfanilamide, Prontosil, reductive metabolism, conjugate hydrolysis, bacterial metabolites
MeSH terms: Gastrointestinal Microbiome, Bacteria, Pharmaceutical Preparations, Humans, Xenobiotics, Treatment Outcome, Drug-Related Side Effects and Adverse Reactions

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