Probiotic, Prebiotic, or Synbiotic Supplementation in Parkinson’s Disease: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

Abstract – Introduction: Alterations in gut microbiota have been linked to various neurological diseases, including Parkinson’s disease (PD). Modifying the microbiota through probiotics, prebiotics, or synbiotics may help improve symptoms in PD patients. This study aimed to evaluate the efficacy and safety of these supplements in treating PD. Methods: A systematic search was conducted in several databases, including PubMed, EMBASE, Scopus, Cochrane Library, Web of Science, and Google Scholar, until September 2023. No restrictions were placed on language or publication date. Study quality was assessed, and data were analyzed using meta-analysis techniques and narrative synthesis tables. The certainty of evidence was evaluated using GRADE, and trial sequential analysis was performed for primary outcomes. Results: Out of 3, 608 studies identified, 69 were selected for review, with 16 analyzed qualitatively. Among these, 12 were randomized controlled trials, and 9 were included in the meta-analysis. Compared with the placebo group, the intervention group would improve non-motor symptoms related to constipation (weekly stools [MD]: 1.04; 95% CI: 0.83, 1.25; Bristol scale [MD]: 0.54; 95% CI: 0.38, 0.70; frequency of laxative use [MD]: −0.63; 95% CI: −0.94, −0.33) and could improve motor symptoms (UPDRS-III [MD]: −2.23; 95% CI: −5.00; 0.53), with very low certainty both due to indirectness and significant risk of bias. Conclusion: With very low to moderate certainty, probiotics, prebiotics, and synbiotics may improve constipation and motor symptoms in PD compared to placebo. These findings suggest a potential benefit, but more high-quality research is needed to confirm these effects and establish stronger evidence.