McGovern Abigail S, Hamlin Adam S, Winter Gal
School of Science and Technology, University of New England, Armidale, NSW, Australia.
Aust N Z J Psychiatry. 2019 Dec;53(12):1151-1166. doi: 10.1177/0004867419877954. Epub 2019 Sep 26.
Serotonin reuptake inhibitors are the predominant treatment for major depressive disorder. In recent years, the diversity of the gut microbiota has emerged to play a significant role in the occurrence of major depressive disorder and other mood and anxiety disorders. Importantly, the role of the gut microbiota in the treatment of such disorders remains to be elucidated. Here, we provide a review of the literature regarding the effects of physiologically relevant concentrations of serotonin reuptake inhibitors on the gut microbiota and the implications this might have on their efficacy in the treatment of mood disorders.
First, an estimation of gut serotonin reuptake inhibitor concentrations was computed based on pharmacokinetic and gastrointestinal transit properties of serotonin reuptake inhibitors. Literature regarding the in vivo and in vitro antimicrobial properties of serotonin reuptake inhibitors was gathered, and the estimated gut concentrations were examined in the context of these data. Computer-based investigation revealed putative mechanisms for the antimicrobial effects of serotonin reuptake inhibitors.
In vivo evidence using animal models shows an antimicrobial effect of serotonin reuptake inhibitors on the gut microbiota. Examination of the estimated physiological concentrations of serotonin reuptake inhibitors in the gastrointestinal tract collected from in vitro studies suggests that the microbial community of both the small intestine and the colon are exposed to serotonin reuptake inhibitors for at least 4 hours per day at concentrations that are likely to exert an antimicrobial effect. The potential mechanisms of the effect of serotonin reuptake inhibitors on the gut microbiota were postulated to include inhibition of efflux pumps and/or amino acid transporters.
This review raises important issues regarding the role that gut microbiota play in the treatment of mood-related behaviours, which holds substantial potential clinical outcomes for patients suffering from major depressive disorder and other mood-related disorders.
5-羟色胺再摄取抑制剂是治疗重度抑郁症的主要药物。近年来，肠道微生物群的多样性在重度抑郁症以及其他情绪和焦虑症的发生中发挥了重要作用。重要的是，肠道微生物群在这类疾病治疗中的作用仍有待阐明。在此，我们综述了关于生理相关浓度的5-羟色胺再摄取抑制剂对肠道微生物群的影响及其对情绪障碍治疗效果可能产生的影响的文献。
首先，根据5-羟色胺再摄取抑制剂的药代动力学和胃肠道转运特性计算肠道中5-羟色胺再摄取抑制剂的浓度。收集了关于5-羟色胺再摄取抑制剂体内和体外抗菌特性的文献，并结合这些数据对估算的肠道浓度进行了研究。基于计算机的调查揭示了5-羟色胺再摄取抑制剂抗菌作用的潜在机制。
使用动物模型的体内证据表明5-羟色胺再摄取抑制剂对肠道微生物群有抗菌作用。对体外研究收集的胃肠道中5-羟色胺再摄取抑制剂的估计生理浓度的检查表明，小肠和结肠的微生物群落每天至少有4小时暴露于可能产生抗菌作用浓度的5-羟色胺再摄取抑制剂中。5-羟色胺再摄取抑制剂对肠道微生物群作用的潜在机制被假定包括抑制外排泵和/或氨基酸转运体。
本综述提出了关于肠道微生物群在治疗情绪相关行为中所起作用的重要问题，这对患有重度抑郁症和其他情绪相关障碍的患者具有重大潜在临床意义。
