To evaluate the bidirectional association between Parkinson’s disease (PD) and celiac disease (CD) through meta-analysis, and to explore molecular mechanisms that may link gut and brain pathology.

The gut-brain axis is increasingly recognized in the pathogenesis of neurodegenerative and autoimmune diseases. PARK7, a multifunctional protein involved in oxidative stress response, immune regulation, and epithelial barrier maintenance, has been implicated in both PD and CD. Elevated PARK7 expression in the duodenal mucosa of children with untreated CD suggests its involvement in intestinal inflammation and barrier dysfunction.

A systematic review identified seven cohort studies published between 2007 and 2024 examining the association between PD and CD. Binary outcome meta-analysis was performed using the Mantel-Haenszel method with a random effects model (DerSimonian-Laird estimator). Risk ratios (RR) were calculated, and heterogeneity was assessed using τ², I², and Cochran’s Q. Subgroup analyses were conducted for PD→CD and CD→PD directions. Publication bias was evaluated using Egger’s test, Begg’s test, trim-and-fill analysis, and fail-safe N methods.

Four studies examined PD→CD and three examined CD→PD. For PD→CD, 38 events occurred among 54,001 PD patients vs. 149 among 138,494 controls. For CD→PD, 254 events occurred among 58,159 CD patients vs. 1,134 among 327,171 controls. The pooled risk ratio was 0.11 (95% CI: -0.01 to 0.23), p = 0.09, with low heterogeneity (I² = 0%). Subgroup estimates were: PD→CD = -0.03 (95% CI: -0.43 to 0.36), CD→PD = 0.12 (95% CI: -0.009 to 0.26). One potentially missing study was identified, with minimal impact on effect size.

The current study supports a modest bidirectional association between PD and CD. The increased expression of PARK7 in CD and its known role in PD pathophysiology highlight it as a potential molecular link in the gut-brain axis.