Gut Microbiota and Metabolites: Orchestrating Depression Pathogenesis Through the Microbiota–Gut–Brain Axis’s Neural, Immune, and Metabolic Routes

Abstract

Depression (major depressive disorder, MDD) is a globally prevalent, highly disabling, and complex mental disorder whose pathogenesis has not been fully elucidated. In recent years, the role of the gut microbiota in depression via the “microbiota–gut–brain axis” (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—neural, immune, and metabolic—thereby 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.