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

Autor: Ricaurte D; Department of Systems Biology, Columbia University, New York, NY, USA.; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University, New York, NY, USA., Huang Y; Department of Systems Biology, Columbia University, New York, NY, USA.; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University, New York, NY, USA., Sheth RU; Department of Systems Biology, Columbia University, New York, NY, USA.; Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University, New York, NY, USA., Gelsinger DR; Department of Systems Biology, Columbia University, New York, NY, USA., Kaufman A; Department of Systems Biology, Columbia University, New York, NY, USA., Wang HH; Department of Systems Biology, Columbia University, New York, NY, USA. harris.wang@columbia.edu.; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA. harris.wang@columbia.edu.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2024 Feb; Vol. 9 (2), pp. 561-575. Date of Electronic Publication: 2024 Jan 17.
DOI: 10.1038/s41564-023-01581-x
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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