APC Microbiome Ireland, University College Cork, Cork, Ireland.
Department of Anatomy and Neuroscience, University College Cork, Room 3.86, Western Gateway Building, Cork, Ireland.
Psychopharmacology (Berl). 2019 May;236(5):1671-1685. doi: 10.1007/s00213-018-5006-5. Epub 2018 Aug 28.
Growing evidence supports a role for the microbiota in regulating gut-brain interactions and, thus, psychiatric disorders. Despite substantial scientific efforts to delineate the mechanism of action of psychotropic medications at a central nervous system (CNS) level, there remains a critical lack of understanding on how these drugs might affect the microbiota and gut physiology.
We investigated the antimicrobial activity of psychotropics against two bacterial strain residents in the human gut, Lactobacillus rhamnosus and Escherichia coli. In addition, we examined the impact of chronic treatment with these drugs on microbiota and intestinal parameters in the rat.
In vitro fluoxetine and escitalopram showed differential antimicrobial effects. Lithium, valproate and aripiprazole administration significantly increased microbial species richness and diversity, while the other treatments were not significantly different from controls. At the genus level, several species belonging to Clostridium, Peptoclostridium, Intestinibacter and Christenellaceae were increased following treatment with lithium, valproate and aripiprazole when compared to the control group. Animals treated with escitalopram, venlafaxine, fluoxetine and aripiprazole exhibited an increased permeability in the ileum.
These data show that psychotropic medications differentially influence the composition of gut microbiota in vivo and that fluoxetine and escitalopram have specific antimicrobial activity in vitro. Interestingly, drugs that significantly altered gut microbial composition did not increase intestinal permeability, suggesting that the two factors are not causally linked. Overall, unravelling the impact of psychotropics on gastrointestinal and microbiota measures offers the potential to provide critical insight into the mechanism of action and side effects of these medications.
越来越多的证据表明，微生物群在调节肠道-大脑相互作用以及精神疾病方面发挥着作用。尽管科学界为了在中枢神经系统 (CNS) 层面阐明精神药物的作用机制付出了巨大努力，但人们对于这些药物如何影响微生物群和肠道生理学仍知之甚少。
我们研究了精神药物对两种人类肠道常驻细菌菌株（鼠李糖乳杆菌和大肠杆菌）的抗菌活性。此外，我们还研究了这些药物的慢性治疗对大鼠肠道微生物群和肠道参数的影响。
氟西汀和艾司西酞普兰在体外表现出不同的抗菌作用。锂、丙戊酸和阿立哌唑的给药显著增加了微生物物种丰富度和多样性，而其他治疗与对照组相比没有显著差异。在属水平上，与对照组相比，锂、丙戊酸和阿立哌唑治疗后，几种属于梭菌属、粪拟杆菌属、真杆菌属和 Christenellaceae 的物种增加。与对照组相比，服用艾司西酞普兰、文拉法辛、氟西汀和阿立哌唑的动物回肠通透性增加。
这些数据表明，精神药物在体内以不同的方式影响肠道微生物群的组成，氟西汀和艾司西酞普兰在体外具有特定的抗菌活性。有趣的是，显著改变肠道微生物组成的药物并没有增加肠道通透性，这表明这两个因素没有因果关系。总的来说，揭示精神药物对胃肠道和微生物群指标的影响，有可能为这些药物的作用机制和副作用提供关键的见解。
