Efficacy and safety of fecal microbiota transplantation in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials with GRADE assessment

Clinical Snapshot

Key Findings

• P Value: P = 0.044

• Effect Size: Mean difference: -2.19 points (favouring FMT)

• Primary Outcome: MDS-UPDRS Part II (motor aspects of daily living) at one month post-FMT

• Nnt Or Sensitivity: No NNT calculable from continuous outcome data; the mean difference of -2.19 on MDS-UPDRS Part II is of borderline clinical significance given that the minimal clinically important difference is approximately 2.5–3.0 points. No significant effects detected for MDS-UPDRS Part III, aggregate MDS-UPDRS, non-motor symptoms, or PDQ-39 quality of life at any time point.

• Confidence Interval: 95% CI: -4.32 to -0.06

Clinical Application

FMT delivery via colonoscopy or nasojejunal tube requires specialist gastroenterology infrastructure and procedural expertise. Oral capsule formulations offer a more accessible route but standardisation of preparation, donor screening, and dosing remains inconsistent across centres. Donor screening protocols add logistical and cost burden. The intervention is not currently part of standard PD management pathways in any jurisdiction. In Australia, FMT is regulated by the Therapeutic Goods Administration (TGA) as a biological product. It currently holds regulatory approval only for recurrent Clostridioides difficile infection. Use in PD would constitute off-label application requiring institutional ethics approval or clinical trial registration. The PBS does not subsidise FMT for neurological indications. RACGP and Neurology Society of Australia guidelines do not currently endorse FMT for PD management. Australian clinicians should counsel patients that FMT for PD remains investigational, with no demonstrated sustained clinical benefit and an evidence base insufficient to support routine use outside registered clinical trials. Adults with established Parkinson's disease, particularly those with concurrent gut microbiome dysbiosis or significant gastrointestinal symptoms (e.g., constipation). The evidence base does not yet permit stratification by PD stage, age, or specific microbiome profile.

Abstract

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease that is a growing public health challenge. Recent evidence showed that gut microbiota dysbiosis is involved in the pathogenesis of PD, prompting interest in fecal microbiota transplantation (FMT) as a potential disease-modifying intervention. This systematic review and meta-analysis aim to evaluate the efficacy and safety of FMT in patients with PD. METHODS: We conducted a systematic literature review using PubMed, Scopus, Web of Science, and the Cochrane Library till June 4, 2026, to identify RCTs comparing FMT with placebo or control interventions in PD. After removal of duplicates alongside title and abstract screening, followed by full-text screening, seven randomized controlled trials were included in this systematic review and meta-analysis. RESULTS: A total of seven randomized controlled trials (RCTs) with 318 subjects were analyzed. FMT was delivered via oral capsules, nasojejunal tubes, or colonoscopy, with follow-up periods ranging from 12 to 52 weeks. The meta-analysis indicated a notable short-term enhancement in daily motor activities, as assessed by MDSUPDRS Part II, after one month (mean difference - 2.19, 95% confidence interval - 4.32 to -0.06; P = 0.044). Nevertheless, no significant estimates were noted for MDS-UPDRS Part III, aggregate MDS-UPDRS scores, motor complications, non-motor symptoms, or overall life quality at any assessed time frame. Some individual studies reported gains in cognitive ability, anxious feelings, quality of life related to constipation, and certain PDQ-39 categories, although these improvements were not uniformly observed. Overall, FMT was well tolerated by participants, with adverse reactions mostly comprising mild, self-resolving gastrointestinal issues and no major safety risks. CONCLUSIONS: FMT is a safe treatment for individuals with PD and may offer modest short-term advantages in performing daily motor tasks. However, current evidence does not indicate lasting enhancements in overall motor capabilities, non-motor symptoms, or life quality. More extensive and sufficiently powered trials utilizing standardized FMT procedures and longer observation periods are necessary to elucidate the therapeutic benefits of FMT in Parkinson's disease.

References

1. 1.Siam, A. M., Moubarak, E. S., Mahmoud, N.-E., Khelifa, H., Aljalawy, F., Hassan, A. A., Ahmed, N. A. T., Wagdy, M., Heikal, Y., & Abbas, O. F. (2025). Efficacy and safety of fecal microbiota transplantation in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials with GRADE assessment. Frontiers in Neuroscience. https://doi.org/10.3389/fnins.2025.1639911