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揭开抗抑郁药对肠道共生微生物的抗菌作用之谜。

Unravelling the antimicrobial action of antidepressants on gut commensal microbes.

机构信息

NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.

Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

出版信息

Sci Rep. 2020 Oct 21;10(1):17878. doi: 10.1038/s41598-020-74934-9.

DOI:10.1038/s41598-020-74934-9
PMID:33087796
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7578019/
Abstract

Over the past decade, there has been increasing evidence highlighting the implication of the gut microbiota in a variety of brain disorders such as depression, anxiety, and schizophrenia. Studies have shown that depression affects the stability of gut microbiota, but the impact of antidepressant treatments on microbiota structure and metabolism remains underexplored. In this study, we investigated the in vitro antimicrobial activity of antidepressants from different therapeutic classes against representative strains of human gut microbiota. Six different antidepressants: phenelzine, venlafaxine, desipramine, bupropion, aripiprazole and (S)-citalopram have been tested for their antimicrobial activity against 12 commensal bacterial strains using agar well diffusion, microbroth dilution method, and colony counting. The data revealed an important antimicrobial activity (bacteriostatic or bactericidal) of different antidepressants against the tested strains, with desipramine and aripiprazole being the most inhibitory. Strains affiliating to most dominant phyla of human microbiota such as Akkermansia muciniphila, Bifidobacterium animalis and Bacteroides fragilis were significantly altered, with minimum inhibitory concentrations (MICs) ranged from 75 to 800 μg/mL. A significant reduction in bacterial viability was observed, reaching 5 logs cycle reductions with tested MICs ranged from 400 to 600 μg/mL. Our findings demonstrate that gut microbiota could be altered in response to antidepressant drugs.

摘要

在过去的十年中,越来越多的证据表明肠道微生物群与多种脑部疾病(如抑郁症、焦虑症和精神分裂症)有关。研究表明,抑郁症会影响肠道微生物群的稳定性,但抗抑郁药物对微生物群结构和代谢的影响仍未得到充分探索。在这项研究中,我们调查了不同治疗类别的抗抑郁药对代表人类肠道微生物群的菌株的体外抗菌活性。六种不同的抗抑郁药:苯乙肼、文拉法辛、去甲丙咪嗪、安非他酮、阿立哌唑和(S)-西酞普兰,针对 12 种共生细菌菌株进行了琼脂孔扩散、微量稀释法和菌落计数的抗菌活性测试。数据显示,不同的抗抑郁药对测试菌株具有重要的抗菌活性(抑菌或杀菌),其中去甲丙咪嗪和阿立哌唑的抑制作用最强。与人体微生物群的大多数优势菌群(如阿克曼氏菌属、双歧杆菌属和脆弱拟杆菌属)相关的菌株明显改变,最小抑菌浓度(MIC)范围为 75 至 800μg/ml。观察到细菌活力显著降低,用测试的 MIC(400 至 600μg/ml)处理后,细菌减少了 5 个对数周期。我们的研究结果表明,肠道微生物群可能会因抗抑郁药物而发生改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/7578019/e2782ca07223/41598_2020_74934_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/7578019/8d322a3a4bf4/41598_2020_74934_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/7578019/e2782ca07223/41598_2020_74934_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/7578019/8d322a3a4bf4/41598_2020_74934_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/7578019/38d57267be71/41598_2020_74934_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/579c/7578019/db9866b8b5dd/41598_2020_74934_Fig3_HTML.jpg
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