Fecal microbiota transplantation in Parkinson’s disease: systematic review and exploratory quantitative synthesis of randomized controlled trials

Abstract

Background: Parkinson’s disease (PD) is increasingly recognized as a multisystem neurodegenerative disorder in which gastrointestinal dysfunction and gut microbiota abnormalities may contribute to symptom burden and progression. Fecal microbiota transplantation (FMT) has emerged as a potential microbiota-targeted intervention, but randomized evidence remains scarce and heterogeneous. A focused synthesis of randomized controlled trials (RCTs) is needed to clarify whether FMT provides clinically meaningful benefits in PD and to better define its safety profile. Objective: To systematically review randomized controlled trials of FMT in PD and perform an exploratory quantitative synthesis of motor, safety, and constipation-related outcomes. Methods: This PRISMA-guided systematic review was prospectively registered in PROSPERO. Randomized controlled trials evaluating FMT in patients with PD and reporting clinical outcomes were included. Data extraction prioritized outcomes suitable for quantitative pooling. Random-effects meta-analyses were performed in Review Manager 5.4.1. Continuous outcomes measured with different but conceptually comparable scales were pooled using standardized mean difference (SMD), whereas outcomes reported on the same scale were pooled using mean difference (MD). Dichotomous safety outcomes were pooled using risk ratios (RR). Risk of bias was assessed using the Cochrane RoB 2 tool. Because of heterogeneity in reporting, only outcomes with sufficiently compatible data were quantitatively synthesized. Results: Six randomized trials were included in the qualitative synthesis. Quantitative pooling was feasible for selected outcomes only. For motor symptoms at approximately 12 weeks, pooling two trials (n=84) showed a significant benefit favoring FMT (SMD =-0.67; 95% CI, -1.12 to -0.23; I² = 0%). For gastrointestinal adverse events, pooling two trials (n=91) showed a higher risk in the FMT group (RR = 3.32; 95% CI, 1.01 to 10.87; I² = 39%). For overall adverse events, pooling two trials (n=42) showed no clear between-group difference (RR = 1.07; 95% CI, 0.52 to 2.21; I² = 38%). For Wexner constipation score, pooling two trials (n=76) showed no significant effect (MD = 0.36; 95% CI, -1.93 to 2.65; I² = 25%). RoB 2 judgments ranged from low risk to high risk, with some concerns in several studies, limiting confidence in pooled estimates. Conclusion: Current randomized evidence suggests that FMT may improve short-term motor outcomes in Parkinson’s disease, but this potential benefit appears to be accompanied by a higher frequency of gastrointestinal adverse events. No clear difference was observed for overall adverse events or Wexner-based constipation severity in the pooled analyses. These findings should be interpreted cautiously because the available evidence is limited by small sample sizes, few studies per outcome, heterogeneity in outcome reporting, and variable risk of bias. Larger, methodologically consistent multicenter RCTs are needed to define the true clinical role of FMT in PD.