Psychiatry Service, Doctor Peset University Hospital, FISABIO, Valencia, Spain (E.M.M.-R., J.M.-R.); Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain (E.M.M.-R., Y.S.); and University of Valencia, Valencia, Spain (J.M.-R.)
Psychiatry Service, Doctor Peset University Hospital, FISABIO, Valencia, Spain (E.M.M.-R., J.M.-R.); Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain (E.M.M.-R., Y.S.); and University of Valencia, Valencia, Spain (J.M.-R.).
Pharmacol Rev. 2024 Aug 15;76(5):956-969. doi: 10.1124/pharmrev.124.001202.
Depression is a highly prevalent disorder and a leading cause of disability worldwide. It has a major impact on the affected individual and on society as a whole. Regrettably, current available treatments for this condition are insufficient in many patients. In recent years, the gut microbiome has emerged as a promising alternative target for treating and preventing depressive disorders. However, the microbes that form this ecosystem do not act alone but are part of a complicated network connecting the gut and the brain that influences our mood. Host cells that are in intimate contact with gut microbes, such as the epithelial cells forming the gut barrier and the immune cells in their vicinity, play a key role in the process. These cells continuously shape immune responses to maintain healthy communication between gut microbes and the host. In this article, we review how the interplay among epithelial cells, the immune system, and gut microbes mediates gut-brain communication to influence mood. We also discuss how advances in our knowledge of the mechanisms underlying the gut-brain axis could contribute to addressing depression. SIGNIFICANCE STATEMENT: This review does not aim to systematically describe intestinal microbes that might be beneficial or detrimental for depression. We have adopted a novel point of view by focusing on potential mechanisms underlying the crosstalk between gut microbes and their intestinal environment to control mood. These pathways could be targeted by well defined and individually tailored dietary interventions, microbes, or microbial metabolites to ameliorate depression and decrease its important social and economic impact.
抑郁症是一种高发疾病，也是全球范围内导致残疾的主要原因。它对患者个体和整个社会都有重大影响。遗憾的是，目前针对这种疾病的治疗方法在许多患者中并不充分。近年来，肠道微生物群已成为治疗和预防抑郁症的有前途的替代靶点。然而，形成这个生态系统的微生物并不是单独作用的，而是连接肠道和大脑的复杂网络的一部分，影响着我们的情绪。与肠道微生物密切接触的宿主细胞，如形成肠道屏障的上皮细胞和附近的免疫细胞，在这个过程中起着关键作用。这些细胞不断塑造免疫反应，以维持肠道微生物和宿主之间的健康沟通。在本文中，我们回顾了上皮细胞、免疫系统和肠道微生物之间的相互作用如何介导肠道-大脑通讯以影响情绪。我们还讨论了我们对肠道-大脑轴机制的认识的进展如何有助于解决抑郁症。
这篇综述的目的不是系统地描述可能对抑郁症有益或有害的肠道微生物。我们通过关注肠道微生物与其肠道环境之间相互作用的潜在机制，采用了一种新颖的观点来控制情绪。这些途径可以通过明确和个体化的饮食干预、微生物或微生物代谢物来靶向，以改善抑郁症并降低其重要的社会和经济影响。
