Articles

The global burden of depression has increased substantially in recent years, making it a major public health problem. Major depressive disorder (MDD) is a multifactorial psychiatric disorder arising from the complex interplay of genetic, environmental, immunological, metabolic, and psychosocial influences. Although the classical monoamine hypothesis has guided antidepressant development for decades, emerging evidence highlights the microbiota-gut-brain (MBG) axis as a pivotal regulator of pathophysiology and a promising target for precision therapeutics. The bidirectional communication between gut microbiota and the central nervous system occurs through interconnected neural, endocrine, immune, and metabolic pathways, influencing emotional regulation, neuroinflammation, and stress responses. Dysbiosis of the gut microbiota is associated with altered microbial metabolites, impaired intestinal barrier integrity, immune activation, and neurotransmitter imbalance, all of which contribute to the onset and progression of MDD. Evidence suggests that altering the gut microbiota will foster the development of effective therapeutic interventions in MDD. Advances in multi-omics technologies have further accelerated the identification of microbiome-derived biomarkers with potential diagnostic, prognostic, and therapeutic value. This article aims to combine mechanistic insights of the MGB axis with clinical applications in MDD to advance biomarker discovery and precision psychiatry.