Extensive impact of non-antibiotic drugs on human gut bacteria

• Published in: Nature (London) 2018-03, Vol.555 (7698), p.623-628
• Main Authors: Maier, Lisa, Pruteanu, Mihaela, Kuhn, Michael, Zeller, Georg, Telzerow, Anja, Anderson, Exene Erin, Brochado, Ana Rita, Fernandez, Keith Conrad, Dose, Hitomi, Mori, Hirotada, Patil, Kiran Raosaheb, Bork, Peer, Typas, Athanasios
• Format: Article
• Language: English
• Subjects: 49/40; 49/47; 49/98; 631/154/1435/2163; 631/326/22; Acids; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Antipsychotic Agents - pharmacology; Antipsychotics; Bacteria; Bacteria - classification; Bacteria - drug effects; Bacteria - growth & development; Bioinformatics; Cohort Studies; Diabetes; Drug Evaluation, Preclinical; Drug interactions; Drug resistance; Drug Resistance, Bacterial - drug effects; Drugs; E coli; Escherichia coli; Gastrointestinal Microbiome - drug effects; Genomes; High-Throughput Screening Assays; Humanities and Social Sciences; Humans; Hypothesis testing; In Vitro Techniques; Intestinal microflora; Microbial Viability - drug effects; Microbiomes; Microbiota; Microbiota (Symbiotic organisms); multidisciplinary; Pharmacological research; Physiological aspects; Psychotropic drugs; Reproducibility of Results; Science; Side effects; Studies; Symbiosis - drug effects
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature25979

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. A screen of more than 1,000 drugs shows that about a quarter of the non-antibiotic drugs inhibit the growth of at least one commensal bacterial strain in vitro . Non-antibiotics with antibiotic effects Some non-antibiotic drugs have been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Athanasios Typas and colleagues screened more than 1,000 marketed drugs and observed that a quarter of them inhibited the growth of at least one bacterial strain in vitro . Scrutiny of previous human cohort studies showed that human-targeted drugs with anticommensal activity have antibiotic-like side effects in humans. The new data provide a resource for future drug-therapy research.