摘要Parkinson's disease has long been considered a disorder that primarily affects the brain,as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containing α-synuclein protein.In recent decades,however,accumulating research has revealed that Parkinson's disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut,called the"gut-brain axis."Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson's disease patients,with findings including impaired intestinal permeability,heightened inflammation,and distinct gut microbiome profiles and metabolites.Furthermore,α-synuclein deposition has been consistently observed in the gut of Parkinson's disease patients,suggesting a potential role in disease initiation.Importantly,individuals with vagotomy have a reduced Parkinson's disease risk.From these observations,researchers have hypothesized that α-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut-brain axis,leading to Parkinson's disease.This review comprehensively examines the gut's involvement in Parkinson's disease,focusing on the concept of a gut-origin for the disease.We also examine the interplay between altered gut-related factors and the accumulation of pathological α-synuclein in the gut of Parkinson's disease patients.Given the accessibility of the gut to both dietary and pharmacological interventions,targeting gut-localized α-synuclein represents a promising avenue for developing effective Parkinson's disease therapies.