High-throughput transcriptomics of 409 bacteria–drug pairs reveals drivers of gut microbiota perturbation
Open accessAbstract
Many drugs can perturb the gut microbiome, potentially leading to negative health consequences. However, mechanisms of most microorganism-drug responses have not been elucidated at the genetic level. Using high-throughput bacterial transcriptomics, we systematically characterized the gene expression profiles of prevalent human gut bacteria exposed to the most frequently prescribed orally administered pharmaceuticals. Across >400 drug-microorganism pairs, significant and reproducible transcriptional responses were observed, including pathways involved in multidrug resistance, metabolite transport, tartrate metabolism and riboflavin biosynthesis. Importantly, we discovered that statin-mediated upregulation of the AcrAB-TolC efflux pump in Bacteroidales species enhances microbial sensitivity to vitamin A and secondary bile acids. Moreover, gut bacteria carrying acrAB-tolC genes are depleted in patients taking simvastatin, suggesting that drug-efflux interactions generate collateral toxicity that depletes pump-containing microorganisms from patient microbiomes. This study provides a resource to further understand the drivers of drug-mediated microbiota shifts for better informed clinical interventions.
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Bacteroides appear particularly susceptible to non-antibiotic toxicities, and agents like simvastatin can downregulate bacterial riboflavin biosynthesis.
“Bacteroides appear particularly susceptible to non-antibiotic toxicities, and agents like simvastatin can downregulate bacterial riboflavin biosynthesis.100”
From Gut dysbiosis in oncology: a risk factor for immunoresistance (2026) · cites this paper as [100]
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Cited by
Sorted by citations
- Authors
- Ricaurte, D., Huang, Y., Sheth, R. U., Gelsinger, D. R., Kaufman, A., & Wang, H. H.
- Affiliations
- Columbia University (US)
- Corresponding author
- Wang, Harris H.
- Venue
- Nature Microbiology
- Published
- 2024-01-17
- Volume
- 9
- Issue
- 2
- Pages
- 561-575
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC11287798
- OpenAlex
- W4390947582
- Cited by
- 38
- References
- 63
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 7
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (DGE 16?44869, 1R21AI146817, 1R01DK118044, 1644869, 2025515)
- Irma T. Hirschl Trust
- National Institutes of Health (DGE1644869, 1016691, MCB-2025515, 1644869)
- Office of Naval Research (N00014-18-1-2237, N00014-17-1, N00014-17-1-2353, N00014)
- National Human Genome Research Institute (RM1HG009490)
- National Cancer Institute (R01CA272898)
- National Institute of Allergy and Infectious Diseases (R21AI146817, R01AI132403)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK118044, P30DK132710)
- National Institute of Biomedical Imaging and Bioengineering (R01EB031935)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- gut microbiota, drug-microbe interactions, bacterial transcriptomics, multidrug resistance, AcrAB-TolC efflux pump, Bacteroidales, statins, simvastatin, vitamin A, secondary bile acids, riboflavin biosynthesis, metabolite transport
- MeSH terms
- Gastrointestinal Microbiome, Anti-Bacterial Agents, Bacteria, Bacterial Proteins, Humans, Gene Expression Profiling
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