Fecal Microbiota Transplantation for Treatment of Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Emerging evidence has indicated gut dysbiosis as a potential modifiable contributor to the pathogenesis of Parkinson's disease (PD). Fecal microbiota transplantation (FMT), a microbiome-centric model aimed at modulating the intestinal microbial taxa, represents a novel therapeutic approach. However, its safety and efficacy profile in improving PD symptoms remains inadequately researched. Methods: PubMed, ScienceDirect, and the Cochrane Central Registry were searched to retrieve relevant articles from inception till February 2025. Risk ratios (RR) and Mean differences (MD), along with 95% confidence intervals (CI), were pooled under the random-effect model for dichotomous and continuous outcomes, respectively. The primary outcomes of interest were change in Movement Disorder Society Unified Parkinson's Disease Rating Scale part 1 (MDS-UPDRS 1), change in MDS-UPDRS 2. Secondary endpoints of interest were change in MDS-UPDRS 3 (on medication), change in MDS-UPDRS 3 (off medication), change in MDS-UPDRS 4, change in Irritable Bowel Severity Scoring System (IBS-SSS), change in Montreal Cognitive Assessment (MoCA), change in Parkinson Disease Questionnaire Summary Index (PDQ-39 SI), and GI adverse events. The Cochrane Risk of Bias 2.0 (RoB 2.0) tool was used for the quality assessment of the included randomized controlled trials (RCTs). A Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment was done for the certainty of evidence. Results: This systematic review and meta-analysis included 145 patients across 3 RCTs. FMT and placebo were comparable regarding the primary outcomes that include MDS-UPDRS Part I (MD = -0.36; 95% CI:[-2.18,1.45]; Conclusion: FMT shows no evidence of superiority compared to placebo. Variations in the findings of existing studies suggest that donor fecal composition, host-microbiota interactions, and methodological heterogeneity may determine outcomes. Further RCTs employing tailored microbiota and standardized endpoint metrics are required to establish a correlation between FMT and PD.