Pharmacological interventions targeting the gut–brain axis in neurological disorders: mechanisms and translational applications

The microbiota–gut–brain axis represents a complex bidirectional communication network linking the gastrointestinal system and the central nervous system and has been increasingly recognized as a key contributor to neurological and psychiatric disorders. Growing evidence indicates that alterations in gut microbiota composition and function can influence brain development and function through neural, immune, endocrine, and metabolic pathways, thereby modulating neuroinflammation, neurotransmission, and blood–brain barrier integrity. Dysregulation of this axis has been implicated in a range of conditions, including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, autism spectrum disorder, depression, anxiety, and stroke. Recent pharmacological advances have identified the microbiota–gut–brain axis as a promising therapeutic target. Current strategies focus on modulating shared pathophysiological mechanisms rather than disease-specific endpoints and include microbiota-directed interventions, immune–inflammatory modulators, neurotransmitter-targeting agents, and approaches aimed at restoring intestinal and blood–brain barrier function. In this review, we summarize the core mechanisms underlying microbiota–gut–brain axis dysfunction and organize existing pharmacological strategies according to their primary targets. By integrating evidence across multiple disorders, we provide a mechanism-oriented framework to support future drug development and precision therapeutic approaches for brain disorders.