Caspani Giorgia, Kennedy Sidney, Foster Jane A, Swann Jonathan
Computational Systems Medicine, Department of Surgery and Cancer, Imperial College London, UK.
Centre for Mental Health and Krembil Research Centre, University Health Network, University of Toronto, Toronto, ON, CA.
Microb Cell. 2019 Sep 27;6(10):454-481. doi: 10.15698/mic2019.10.693.
Gastrointestinal and central function are intrinsically connected by the gut microbiota, an ecosystem that has co-evolved with the host to expand its biotransformational capabilities and interact with host physiological processes by means of its metabolic products. Abnormalities in this microbiota-gut-brain axis have emerged as a key component in the pathophysiology of depression, leading to more research attempting to understand the neuroactive potential of the products of gut microbial metabolism. This review explores the potential for the gut microbiota to contribute to depression and focuses on the role that microbially-derived molecules - neurotransmitters, short-chain fatty acids, indoles, bile acids, choline metabolites, lactate and vitamins - play in the context of emotional behavior. The future of gut-brain axis research lies is moving away from association, towards the mechanisms underlying the relationship between the gut bacteria and depressive behavior. We propose that direct and indirect mechanisms exist through which gut microbial metabolites affect depressive behavior: these include (i) direct stimulation of central receptors, (ii) peripheral stimulation of neural, endocrine, and immune mediators, and (iii) epigenetic regulation of histone acetylation and DNA methylation. Elucidating these mechanisms is essential to expand our understanding of the etiology of depression, and to develop new strategies to harness the beneficial psychotropic effects of these molecules. Overall, the review highlights the potential for dietary interventions to represent such novel therapeutic strategies for major depressive disorder.
胃肠道功能与中枢功能通过肠道微生物群内在相连，肠道微生物群是一个与宿主共同进化的生态系统，其生物转化能力得以扩展，并通过代谢产物与宿主生理过程相互作用。微生物-肠道-脑轴的异常已成为抑郁症病理生理学的关键组成部分，促使更多研究试图了解肠道微生物代谢产物的神经活性潜力。本综述探讨了肠道微生物群导致抑郁症的可能性，并重点关注微生物衍生分子——神经递质、短链脂肪酸、吲哚、胆汁酸、胆碱代谢物、乳酸和维生素——在情绪行为中的作用。肠道-脑轴研究的未来在于从关联性研究转向探究肠道细菌与抑郁行为之间关系的潜在机制。我们提出，肠道微生物代谢产物影响抑郁行为存在直接和间接机制：这些机制包括（i）直接刺激中枢受体，（ii）外周刺激神经、内分泌和免疫介质，以及（iii）组蛋白乙酰化和DNA甲基化的表观遗传调控。阐明这些机制对于拓展我们对抑郁症病因的理解以及开发利用这些分子有益精神作用的新策略至关重要。总体而言，本综述强调了饮食干预作为重度抑郁症新型治疗策略的潜力。
