Abstract
Growing evidence has suggested that the gut-brain axis plays an important role in the pathogenesis of Parkinson's disease (PD), and that this role is mediated by the interactions between bile acids (BAs) and intestinal microbiota. Given that cholecystectomy can lead to alterations in BAs and gut microbiota, we investigated whether cholecystectomy is linked to a higher risk of PD. We constructed a cohort of patients with an operation code of cholecystectomy from 2010 to 2015 (n = 161,838) and age- and sex-matched control subjects without cholecystectomy (n = 286,135) using the National Health Insurance Service database. Incident PD was traced over a maximum observation period of 7 years. We identified 1404 incident PD cases during 1,631,265 person-years of follow-up. The cholecystectomy group showed an elevated risk of PD compared to the control group, even after adjusting for potential confounding factors (adjusted hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.02-1.27). When the data were split by sex, the risk elevation was significant in men (adjusted HR 1.22, 95% CI 1.06-1.41), but not in women (adjusted HR 1.03, 95% CI 0.88-1.22). Our results provide evidence that cholecystectomy is associated with an increased risk of developing PD. This association differed between men and women, suggesting sex-specific effects of cholecystectomy on the risk of PD.