Extensive impact of non-antibiotic drugs on human gut bacteria
Open accessAbstract
A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future research on drug-microbiome interactions, opening new paths for side effect control and drug repurposing, and broadening our view of antibiotic resistance.
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The human gut microbiome is influenced by diet and medication use.
“The human gut microbiome is itself shaped by a wide variety of environmental exposures, including diet (8, 9) and medication use (10–13)”
From Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response (2021) · cites this paper as [10]
Medication usage is a significant but minor contributor (R2 = 0.003) to microbial community composition.
“Despite this, medication usage was a significant, albeit minor, contributor (R2 = 0.003) to microbial community composition, highlighting how xenobiotics can and do influence the gut microbiome (Jackson et al., 2018; Maier et al., 2018).”
From Gut microbiome stability and dynamics in healthy donors and patients with non-gastrointestinal cancers (2021) · cites this paper as Maier et al., 2018
In a study of more than 1,000 clinically used drugs tested against many human gut commensals, nearly one quarter had antibiotic-like side effects.
“In a recent examination of over 1,000 clinically used drugs and their impact on a broad selection of human gut commensals, nearly a quarter demonstrated antibiotic-like side effects59.”
From Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential (2018) · cites this paper as [59]
24% of drugs with human targets across therapeutic classes inhibited the growth of at least one bacterial strain in vitro.
“24% of the drugs with human targets across therapeutic classes inhibited the growth of at least one bacterial strain in vitro.”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Maier et al., 2018
The Maier et al. screen largely focused on in vitro antibacterial activity of each drug against one representative bacterial strain per species, so implications for more complex bacterial communities need to be considered.
“Although the study largely focused on the in vitro antibacterial activity of each drug screened against one representative bacterial strain per species, the implications for more complex bacterial communities need to be considered.”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Maier et al., 2018
Metformin appears to have a dose-dependent antimicrobial effect with inhibition of specific bacterial strains only apparent at physiologic intestinal concentrations.
“Metformin appears to have a dose-dependent antimicrobial effect with inhibition of specific bacterial strains only apparent once tested at physiologic intestinal concentrations (Maier et al., 2018).”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Maier et al., 2018
In a screen of over 1000 commonly prescribed non-antibiotic drugs, nearly a quarter demonstrated antibiotic-like activity, significantly inhibiting growth of at least one human commensal.
“In a recent study that screened over 1000 commonly prescribed non-antibiotic drugs for their impact on a broad selection of human gut commensals, nearly a quarter of the tested medications demonstrated antibiotic-like activity, significantly inhibiting the growth of at least one human commensal159.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [159]
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- Authors
- Maier, L., Pruteanu, M., Kuhn, M., Zeller, G., Telzerow, A., Anderson, E. E., Brochado, A. R., Fernandez, K. C., Dose, H., Mori, H., Patil, K. R., Bork, P., & Typas, A.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Nara Institute of Science and Technology (JP)
- Corresponding author
- Zeller, Georg
- Patil, Kiran Raosaheb
- Typas, Athanasios
- ORCID
- Venue
- Nature
- Published
- 2018-03-19
- Volume
- 555
- Issue
- 7698
- Pages
- 623-628
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6108420
- OpenAlex
- W2792021903
- Cited by
- 1,905
- References
- 63
- Citations by year
- 2026: 202 · 2025: 197 · 2024: 202 · 2023: 241 · 2022: 219 · 2021: 245 · 2020: 252 · 2019: 231 · 2018: 114
- FWCI
- 74.22
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (16H02485)
- 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
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Keywords
- non-antibiotic drugs, gut microbiota, drug-microbiome interactions, antibiotic resistance, antipsychotic drugs, bacterial growth inhibition, commensal bacteria, adverse drug reactions, drug repurposing
- MeSH terms
- Gastrointestinal Microbiome, Anti-Bacterial Agents, Bacteria, Drug Evaluation, Preclinical, Humans, Symbiosis, Antipsychotic Agents, Reproducibility of Results, Cohort Studies, Drug Resistance, Bacterial, Microbial Viability, High-Throughput Screening Assays, In Vitro Techniques
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