Modulating depression through the gut-brain axis: the role of gut microbiota in therapeutic interventions

Depression is a multifactorial mental disorder increasingly linked to gut microbiota through the microbiota-gut-brain axis (MGBA). This review aims to explore how alterations in gut microbial composition influence depressive symptoms via neurochemical, immunological, and neuroendocrine pathways. Key mechanisms include microbial modulation of serotonin, dopamine, and GABA levels; systemic inflammation; hypothalamic-pituitary-adrenal (HPA) axis dysregulation; and vagus nerve signaling. Emerging evidence suggests that gut microbiota may also influence the efficacy of selective serotonin reuptake inhibitors (SSRIs), potentially via vagal pathways. Additionally, a distinct microbial signature has been observed in individuals with depression, with therapeutic probiotics targeting this dysbiosis showing beneficial effects. This review further evaluates the therapeutic potential of probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions in managing depression. We highlight the need for microbiota-based biomarkers and personalized interventions in future clinical applications. Overall, this review underscores the therapeutic relevance of targeting the gut-brain axis in depression treatment.