Decoding the gut-brain axis in depression: mechanistic insights and functional microbiota-based interventions

Abstract

The gut-brain axis has emerged as a critical research focus at the intersection of microbiology, nutrition, and neuropsychiatry, underscoring the complex, bidirectional communication between the gastrointestinal tract and the central nervous system. Accumulating evidence suggests that the gut microbiota plays a pivotal role in the development and potential mitigation of depression through multiple physiological pathways. This review systematically summarizes current advances in understanding how the gut microbiota influences depressive symptoms, with particular attention to mechanisms involving neurotransmitter metabolism, immune system modulation, and hypothalamic-pituitary-adrenal axis regulation. Additionally, the microbial production of neuroactive metabolites and the signaling roles of short-chain fatty acids, indoles, and bile acid derivatives in mood regulation were discussed. The bidirectional nature of gut-brain communication is further explored through the lens of microbial-host interaction, emphasizing how probiotics, prebiotics, and microbial biomarkers modulate gut-brain signaling pathways. Finally, the review outlines emerging strategies and future directions in microbiota-targeted interventions for depression, providing a scientific basis for the development of functional food approaches in mental health management.