High-throughput transcriptomics of 409 bacteria-drug pairs reveals drivers of gut microbiota perturbation

作者：Deirdre Ricaurte, Yiming Huang, Ravi U. Sheth, D. Gelsinger, A. Kaufman, Harris H. Wang · 发表于：Nature Microbiology · 年份：2024 · DOI：10.1038/s41564-023-01581-x · 研究领域：Medicine

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. High-throughput bacterial transcriptomics of 409 drug–microorganism interactions reveals mechanistic insights into drug-mediated microbiota shifts.