The Brain-Gut-Microbiome Axis: Exploring the Link Between Depression and Irritable Bowel Syndrome.

The brain-gut-microbiome system is an integrated communication network linking the central nervous system, enteric nervous system, immune pathways, and intestinal microbiota. Increasing evidence indicates that dysregulation of this bidirectional signaling system contributes to both gastrointestinal and psychiatric disorders. Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, and major depressive disorder (MDD) frequently coexist and share multiple biological and environmental risk factors. Advances in microbiome science, neuroimaging, and multi-omics technologies have revealed that microbial metabolites, neuroimmune signaling, and stress-responsive neuroendocrine pathways influence neural circuits regulating mood, visceral perception, and gastrointestinal function. These interconnected mechanisms may explain the high comorbidity between IBS and MDD and suggest that both conditions arise from disturbances across overlapping biological systems. In this review, we synthesize current knowledge of genetic, neurobiological, and potential microbial contributors to IBS and depression, discuss emerging therapeutic approaches targeting the brain-gut-microbiome system, and highlight future directions for developing mechanistically informed treatment strategies.