Extensive impact of non-antibiotic drugs on human gut bacteria

Nature. 2018 Mar 29;555(7698):623-628. doi: 10.1038/nature25979. Epub 2018 Mar 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antipsychotic Agents / pharmacology
  • Bacteria / classification
  • Bacteria / drug effects*
  • Bacteria / growth & development
  • Cohort Studies
  • Drug Evaluation, Preclinical*
  • Drug Resistance, Bacterial / drug effects*
  • Gastrointestinal Microbiome / drug effects*
  • High-Throughput Screening Assays
  • Humans
  • In Vitro Techniques
  • Microbial Viability / drug effects
  • Reproducibility of Results
  • Symbiosis / drug effects

Substances

  • Anti-Bacterial Agents
  • Antipsychotic Agents