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In recent years, the role of the gut microbiota in depression via the \u201cmicrobiota\u2013gut\u2013brain axis\u201d (MGB axis) has attracted increasing attention. A large body of evidence indicates that the gut microbiota and its metabolites can engage in bidirectional communication with the central nervous system through three core pathways\u2014neural, immune, and metabolic\u2014thereby profoundly influencing the onset and progression of depression. This article reviews the specific mechanisms by which the gut microbiota affects depression through the aforementioned pathways, including regulating the balance of neurotransmitters (e.g., GABA and 5-HT), mediating neuroinflammatory responses, and adjusting the levels of metabolites such as short-chain fatty acids. This study aims to provide a theoretical basis for an in-depth understanding of the pathophysiological mechanisms of depression and the development of novel microbiota-based intervention therapeutic strategies.<\/jats:p>","DOI":"10.3390\/biom16091225","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:03:41Z","timestamp":1787558621000},"page":"1225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbiota and Metabolites: Orchestrating Depression Pathogenesis Through the Microbiota\u2013Gut\u2013Brain Axis\u2019s Neural, Immune, and Metabolic Routes"],"prefix":"10.3390","volume":"16","author":[{"given":"Zhen-Zhen","family":"Dong","sequence":"first","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China"},{"name":"Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou 310015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuojie","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2001-6187","authenticated-orcid":false,"given":"Qingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China"},{"name":"Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou 310015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jad.2018.09.015","article-title":"Adolescent and adult differences in major depression symptom profiles","volume":"243","author":"Rice","year":"2019","journal-title":"J. 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