Neurological diseases associated with gut–brain axis: pathophysiology, clinical implications, and therapeutics

The brain–gut axis, first described in the 19th century, refers to the complex bidirectional communication network between the central nervous system and the gastrointestinal tract. This dynamic system operates through neuronal, endocrine, and immune pathways. It has since expanded to include the influence of gut microbiota, given its significant role in gut motility disorders and neurological diseases. The intricate relationship involves multiple signaling mechanisms, including toll-like receptors, nuclear factor-kappa B, α-synuclein, the hypothalamic–pituitary–adrenal axis, and vagal signaling. Dysregulation of the brain–gut axis has been implicated in numerous neurological conditions, including Parkinson’s disease, stroke, multiple sclerosis, autism spectrum disorder, spinal cord injury, and peripheral neuropathies, many of which present with well-recognized gastrointestinal manifestations. Conversely, neurological sequelae are frequently associated with primary gastrointestinal disorders such as inflammatory bowel disease, celiac disease, and hepatic failure. This narrative literature review aims to examine the epidemiology, clinical presentation, and pathogenesis of common neurological and gastrointestinal diseases through the lens of the brain–gut axis. By highlighting the interconnected metabolic, immune, and physiological mechanisms underlying these conditions, this review seeks to promote a more integrated understanding of disease processes and to support improved diagnostic strategies, therapeutic approaches, and long-term patient outcomes.