357PHARMACOLOGICAL MODULATION OF THE GUT–BRAIN AXIS: IMPLICATIONS FOR MENTAL HEALTH DISORDERS.The gut–brain axis (GBA) is a complex bidirectional network integrating the gastrointestinal tract, enteric nervous system, immune system, endocrine signaling, and the central nervous system. The intestinal microbiota constitutes a dynamic “metabolic organ” capable of influencing neurodevelopment, stress responsivity, neurotransmission, immune activation, and systemic metabolism. Increasing evidence supports a causal contribution of gut microbial dysbiosis to major depressive disorder, anxiety disorders, bipolar disorder, schizophrenia spectrum illness, and stress-related conditions. Mechanistically, microbiome-derived metabolites, bacterial cell wall components such as lipopolysaccharide, and immune mediators such as interleukin-6 and tumor necrosis factor-alpha may shape neuroinflammation, blood–brain barrier integrity, and hypothalamic– pituitary–adrenal axis activation. Pharmacological modulation of the gut microbiome represents a promising translational approach in neuropsychiatry. Microbiome-targeted strategies include probiotics (“psychobiotics”), prebiotics, synbiotics, postbiotics, dietary polyphenols, bile-acid modulators, antibiotics, and fecal microbiota transplantation. Additionally, conventional psychotropic drugs exert secondary effects on microbial composition and metabolic output. This review critically synthesizes mechanistic and clinical evidence supporting pharmacological manipulation of the GBA as a therapeutic avenue for psychiatric disorders, highlights limitations in current trial methodology, and proposes future directions including precision psychobiotics, microbial metabolite therapeutics, and biomarker-driven personalized psychiatrylgopipharma10@gmail.comResearch1622026 Gut–Brain Axis, Microbiome, Psychobiotics, Depression, Anxiety.Yogendra Shanth S1*, Saranya P2, Dr. Kalvimoorthi V3, Gopi LM. Pharm, First Year, Aadhi Bhagawan College of Pharmacy, Rantham, Tiruvannamalai, Tamil Nadu, India