The role of gut brain axis in the pathogenesis of Parkinson's disease

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder traditionally characterized by dopaminergic neuronal loss and α-synuclein aggregation within the central nervous system. However, increasing evidence suggests that the disease may originate outside the brain, particularly within the gastrointestinal tract, through mechanisms involving the microbiota–gut–brain axis (MGBA). This article summarizes the interactions between intestinal dysfunction, barrier dysfunction, inflammation, and α- synuclein transmission along the vagus nerve in the pathogenesis of Parkinson's disease. Alterations in microbial composition are closely linked with impaired intestinal barrier integrity, leading to neuroinflammation and dopaminergic neuron degeneration. Clinical studies further support the causal role of gut-derived signals in shaping disease onset and progression. Additionally, intestinal-derived α-synuclein has been demonstrated to propagate retrogradely to the brainstem via the vagus nerve, reinforcing the “gut-origin hypothesis.” By integrating microbiology, neuroscience, and immunology, the study of MGBA not only broadens our understanding of PD etiology but also highlights novel targets for prevention and personalized therapeutic strategies.