(SLB-014) The Effect of Antibiotics on the Risk of Parkinson’s Disease: A Meta-Analysis of Observational Epidemiological Studies

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, leading to motor and non-motor dysfunction. Emerging evidence suggests that gut microbiome alterations may play a role in PD pathogenesis, given the gut-brain axis's involvement in neuroinflammation. Antibiotics (ABs), known to disrupt gut microbiota, have been hypothesized to contribute to PD risk. However, prior epidemiologic studies have yielded conflicting findings.

Objectives: This meta-analysis aimed to evaluate the association between ABs exposure and the risk of PD using published pharmacoepidemiologic studies.

Methods: A systematic literature search was conducted in PubMed, Embase, and Scopus for observational studies assessing the relationship between AB use and PD onset up to January 2025. Eligible studies included case-control and cohort studies, with clearly defined PD outcome and exposure assessments. Two independent reviewers screened titles, abstracts, and full texts for eligibility, performed data extraction, and assessed study quality using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was conducted to calculate pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I² statistics. Subgroup analyses were performed based on antibiotic class and study design. Sensitivity analyses using leave-one-out analysis were conducted to evaluate the robustness of findings. Publication bias was assessed using Egger’s test and funnel plot asymmetry.

Results: A total of six studies met the inclusion criteria, comprising three case-control and three cohort studies. In the random-effects meta-analysis, AB use was not significantly associated with an increased risk of PD (adjusted OR/HR: 1.08, 95% CI 0.92–1.28, I² = 91.4%), indicating substantial heterogeneity across studies. When stratified by study design, the pooled analysis of cohort studies yielded an overall adjusted OR of 1.09 (95% CI 0.86–1.39, I² = 78.2%), while the case-control studies demonstrated a pooled OR of 1.09 (95% CI 0.82–1.45, I² = 92.7%). No antibiotic class was found to be significantly associated with PD risk in the subgroup analysis. Leave-one-out analysis confirmed the stability of the results. Egger’s test and a symmetrical funnel plot indicated no significant publication bias.

Conclusions: This meta-analysis found no significant association between antibiotic use and PD risk. While subgroup analyses showed no clear risk differences across antibiotic classes, substantial heterogeneity was observed. Further well-designed epidemiologic studies and longer follow-up periods are needed to clarify the potential role of antibiotics in PD pathogenesis.