Safety and Efficacy of Fecal Microbiota Transplantation in Alleviating Symptoms of Parkinson's Disease: A Randomized, Placebo‐Controlled, Double‐Blinded Study

OBJECTIVES: Changes in the gut microbiome may be involved in the pathogenesis and progression of Parkinson's disease (PD). This randomized, placebo-controlled, double-blinded study aimed to assess the effects of fecal microbiota transplantation (FMT) on the manifestation of the motor symptoms of PD (The Movement Disorders Society - Unified Parkinson's Disease Rating Scale Part III [MDS-UPDRS III]) over a 12 month long observation and non-motor symptoms as secondary objectives: the Movement Disorders Society-Non-Motor Rating Scale; EuroQol-5 Dimension; PD Quality-of-Life Questionnaire; Montreal Cognitive Assessment (MoCA); UPDRS I, II, and IV; Gastrointestinal Dysfunction Scale for PD; modified Constipation Assessment Scale; and levodopa equivalent dose. METHODS: The patients were randomly assigned to receive either fecal microbiota (Mbiotix, Human Biome Institute) or placebo (auto-fecal microbiota, prepared from the patient's stool) in a 1:1 ratio. The fecal microbiota transplantation was performed via colonoscopy. Assessments were performed before and after 12 months for the MoCA and at 1, 3, 6, and 12 months for the other scales. Intention-to-treat analysis was performed using a multivariable mixed regression model. RESULTS: Of the 59 patients included, 28 were randomly assigned to the Mbiotix group (median age = 65 years; 15 male patients) and 31 to the placebo group (median age = 63 years; 14 male patients). No significant differences were observed in the MDS-UPDRS III "OFF" state score at 12 months between groups (1.50 points, 95% confidence interval [CI] = -4.28 to 7.28, p = 1.00), however, some non-motor symptoms improved in different study timepoints. INTERPRETATION: A single FMT does not influence motor symptoms manifestation in patients with PD but could improve non-motor functioning via gut-brain axis. Trial registration information: Clinical Trial ID NCT05204641 was submitted on November 29, 2021. The first patient was enrolled on January 4, 2022. ANN NEUROL 2026.