Ding Pengbo, Lu Ji, Lei Tong, Guo Yinan, Zhu Baoli, Zhao Yong, Wang Yue, Engelstädter Jan, Schembri Mark A, Guo Jianhua
Australian Centre for Water and Environmental Biotechnology, The University of Queensland, St. Lucia, Queensland, Australia.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Gut Microbes. 2025 Dec;17(1):2514138. doi: 10.1080/19490976.2025.2514138. Epub 2025 Jun 3.
Antibiotic resistance is a global public health challenge. The gut microbiota serves as a reservoir for antibiotic resistance genes (ARGs), facilitating their transfer between bacteria. With the rising incidence of major depressive disorders (MDD), antidepressant prescriptions have surged. Previous pure-culture studies suggest that antidepressants exhibit antibiotic-like side effects, but their impact on gene transfer in microbial communities remains unclear. Here, we report that clinically relevant doses of antidepressants duloxetine and sertraline enhance the transfer of a broad-host range conjugative plasmid across bacterial phyla from mice gut microbiota. Tests in human gut simulators confirmed that duloxetine facilitates plasmid transfer in human gut microbiota. Mechanistic analyses revealed that antidepressants increase reactive oxygen species levels and alter bacterial cell membrane permeability. Using fluorescence-activated cell sorting and 16S rRNA gene sequencing, we discovered that antidepressants alter plasmid transfer patterns at both phylum and genus levels, driving ARG exchange among opportunistic pathogens. Our findings suggest that antidepressant use may promote the spread of antibiotic resistance between commensal and pathogenic bacteria, raising important public health concerns.
抗生素耐药性是一项全球性的公共卫生挑战。肠道微生物群是抗生素耐药基因（ARGs）的储存库，促进了这些基因在细菌之间的转移。随着重度抑郁症（MDD）发病率的上升，抗抑郁药的处方量激增。以往的纯培养研究表明，抗抑郁药具有类似抗生素的副作用，但其对微生物群落中基因转移的影响仍不清楚。在此，我们报告，临床相关剂量的抗抑郁药度洛西汀和舍曲林可增强广泛宿主范围接合质粒在小鼠肠道微生物群不同细菌门类之间的转移。在人体肠道模拟器中的测试证实，度洛西汀可促进人体肠道微生物群中的质粒转移。机制分析表明，抗抑郁药会增加活性氧水平并改变细菌细胞膜通透性。通过荧光激活细胞分选和16S rRNA基因测序，我们发现抗抑郁药在门和属水平上都会改变质粒转移模式，推动机会性病原体之间的ARG交换。我们的研究结果表明，使用抗抑郁药可能会促进共生菌和病原菌之间抗生素耐药性的传播，引发重要的公共卫生问题。
