Colonoscopic fecal microbiota transplantation for Mild-to-Moderate Parkinson’s Disease: A randomized controlled trial

Abstract

OBJECTIVE: Growing evidence supports the efficacy and safety of fecal microbiota transplantation (FMT) in treating Parkinson's disease (PD). Fecal microbiota are commonly transplanted via oral capsules, a nasojejunal tube, or colonoscopy, but freezing often decreases the diversity and viability of transplanted microbiota. This single-center, double-blind, randomized, placebo-controlled trial aims to explore the efficacy and safety of fresh FMT via colonoscopy in dealing with PD. METHODS: Thirty patients with mild-to-moderate PD (Hoehn-Yahr stage I-III) were randomly assigned into the FMT group (fresh FMT via colonoscopy) and placebo group (saline injection via colonoscopy) in a 1:1 ratio. Motor and non-motor symptoms, constipation, quality of life, cognitive function, emotional state and sleep quality were assessed using relevant scales. Fecal samples were harvested before and at 4, 8 and 12 weeks after treatment for metagenomic and metabolomics analyses. RESULTS: A total of 30 patients with mild-to-moderate PD were enrolled in the present study, involving 18 males and 12 females with a median age of 68 years, a median age of onset of 63.5 years, and a median disease duration of 3 years. At 12 weeks, scores of the UPDRS Ⅲ (group × time effect, B = - 8.80 [-13.79, -3.81]), PAC-QOL (group × time effect, B = - 29.67 [-45.35, -13.98]), UPDRS Ⅱ (group × time effect, B = - 5.07 [-8.85, -1.28]), NMSS (group × time effect, B = - 35.60 [-53.59, -17.61]), PDQ-39 (group × time effect, B = - 17.80 [-28.21, -7.39]), HAMA (group × time effect, B = - 1.66 [-2.92, -0.40]), and HAMD (group × time effect, B = - 1.33 [-2.49, -0.16]) were significantly reduced in the FMT group, while CSBM per week (group × time effect, B = 3.03 [1.42, 4.63]) and the Bristol Stool Scale score (group × time effect, B = 1.95 [0.12, 3.79]) significantly increased (all P < 0.05). Significant alterations were seen in the gut microbiota and fecal metabolites in the FMT group. No adverse events were observed during the follow-up period. CONCLUSION: Fresh FMT via colonoscopy is a safe and well-tolerated procedure for treating mild-to-moderate PD. It effectively alleviates motor and non-motor symptoms, thus facilitating defecation and improving the quality of life. These effects can be maintained for a minimum of 12 weeks and may be attributed to the optimization of gut microbiota and fecal metabolites.