Efficacy of gut microbiota-targeted therapies in Parkinson’s disease: a systematic review and meta-analysis of randomized controlled trials

Objective This study aimed to investigate the efficacy of gut microbiota (GM)-targeted therapies in treating Parkinson’s disease (PD). Methods Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane, and WOS from database inception to June 2025. The eligible RCTs employed GM-targeted therapies, including antibiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT), as adjunct treatments for PD. Data were pooled using a random-effects model, and the effect sizes were expressed as standardized mean differences (SMDs). In addition, the quality of evidence for all outcomes was assessed using the GRADE framework. Results This study demonstrated that GM-targeted therapies significantly improved PD outcomes, including Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) III (SMD: -0.34, 95%CI: -0.57 to -0.11, P = 0.004), bowel movements (BMs) (SMD: 1.27, 95%CI: 0.35 to 2.2), use of laxatives (SMD: -0.33, 95% CI: -0.65 to -0.02), malondialdehyde (MDA) (SMD: -0.69, 95%CI: -1.23 to -0.15) indicators. However, there were no significant improvements in MDS-UPDRS I (SMD: -0.64, 95%CI: -1.42 to 0.13), MDS-UPDRS II (SMD: -0.28, 95%CI: -0.70 to 0.14), MDS-UPDRS IV (SMD: -0.08, 95% CI: -0.82 to 0.66), Mini-Mental State Examination (MMSE) (SMD: -0.01, 95% CI: -0.30 to 0.29), Montreal Cognitive Assessment (MoCA) (SMD: 0.04, 95%CI: -0.53 to 0.60), non-motor symptom scale (NMSS) (SMD: -0.11, 95%CI: -0.94 to 0.72), Parkinson’s Disease Questionnaire-39 (PDQ-39) (SMD: -0.19, 95%CI: -0.58 to 0.20), total antioxidant capacity (TAC) (SMD: 0.29, 95%CI: -0.04 to 0.62), glutathione (GSH) (SMD: 0.51, 95%CI: -0.02 to 1.03), and Geriatric Depression Scale-15 (GDS-15) (SMD: -0.37, 95%CI: -0.87 to 0.12). Conclusion GM-targeted therapies may improve motor symptom scores (as measured by MDS-UPDRS III), alleviate constipation, and reduce blood malondialdehyde levels in PD patients. However, they did not significantly impact the scores for cognitive function, PD neuropsychiatric, behavioral, and emotional symptoms, and activities of daily living in this analysis. Given the inherent limitations of the included studies (such as small sample sizes and heterogeneity), future large-scale and rigorously designed RCTs are needed to validate these preliminary findings. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD42024606415.