Long-Term Risk of Parkinson's Disease Following Irritable Bowel Syndrome: A Nationwide Population-Based Cohort Study

Background/Objectives: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder linked to gut-brain axis dysregulation. Gastrointestinal dysfunction has been implicated in the prodromal phase of Parkinson's disease (PD), but long-term population-based evidence remains limited. Methods: Using the Korean National Health Insurance Service database (2012-2023), we conducted a nationwide matched cohort study including 142,668 patients with IBS and 285,336 matched individssuals without IBS. IBS was defined by at least two ICD-10 diagnoses with a three-year washout period to reduce reverse causation. Participants were followed for up to nine years for incident PD. Incidence rate ratios (IRRs), Kaplan-Meier analyses, and multivariable Cox models were applied. Results: IBS was associated with a higher incidence of PD (IRR, 1.24; 95% CI, 1.14-1.36). The magnitude and statistical significance of the association varied across age- and sex-stratified analyses, with the highest crude relative risk observed among women younger than 60 years. In fully adjusted Cox models, IBS remained significantly associated with PD in the overall population (hazard ratio, 1.38; 95% CI, 1.18-1.62), with statistical significance retained particularly among women in subgroup analyses. Sensitivity analyses using alternative definitions yielded consistent results. Conclusions: In this nationwide cohort, IBS was associated with an increased long-term risk of PD after adjustment for measured covariates. Given the observational claims-based design, these findings should be interpreted cautiously as hypothesis-generating epidemiological evidence requiring further validation.