Gut-Brain Axis: The Role of Gastrointestinal Issues in Parkinson's Disease.

Parkinson's Disease (PD) is a complex neurodegenerative disorder traditionally identified by motor symptoms. However, non-motor manifestations such as lower gastrointestinal (GI) disturbances are increasingly recognized as early indicators and contributors to disease progression. This review examines the gut-brain axis and the role of lower GI issues, particularly constipation and gut dysbiosis, in the pathogenesis and management of PD. The "bottom-up" hypothesis suggests that PD may originate in the gut, with misfolded alpha-synuclein aggregating in the enteric nervous system before appearing in the brain. This pathological process is closely associated with gut dysbiosis, which contributes to increased intestinal permeability, systemic inflammation, and neuroinflammation via the vagus nerve and disrupted blood-brain barrier. Dysbiosis not only alters microbial diversity but also leads to the overproduction of neurotoxic metabolites, like lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs). These biochemical changes create a pro-inflammatory environment that accelerates neurodegeneration. The review examines integrative interventions, including dietary strategies such as the Mediterranean diet and supplementation with probiotics, prebiotics, and synbiotics, which have shown promise in modulating gut microbiota and reducing inflammation. Lifestyle factors, such as exercise and stress reduction, also support gut health and symptom management, with structured multimodal exercise regimens showing significant benefit in motor function.