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]; P = .70; I 2 = 33%), Part II (MD = −0.46; 95% CI:[-1.91,0.99]; P = .53; I 2 = 0%). The secondary outcomes, involving MDS-UPDRS Part III on-medication (MD = 1.41; 95% CI:[-2.14,4.42]; P = .50; I 2 = 17%), Part III off-medication (MD = 1.26; 95% CI:[-2.27,4.79]; P = .48; I 2 = 0%), and Part IV (MD = −0.39; 95% CI:[-1.63,0.85]; P = .54; I 2 = 24%) were also comparable between the two groups. No significant changes were observed in IBS-SSS (MD = −15.91; 95% CI:[-63.17,31.89]; P = .51; I 2 = 76%), PDQ-39 SI (MD = −2.13, 95% CI:[-5.62,1.36]; P = .23; I 2 = 0%), and MOCA scores (MD = 0.11; 95% CI:[-1.34,1.57]; P = .88; I 2 = 68%). However, the FMT group had more frequent adverse gastrointestinal events (RR = 3.32; 95% CI: [1.01,10.87]; P = .05; I 2 = 39%). 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.