Core Viewpoint - Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and the accumulation of pathological α-synuclein aggregates. Current treatments primarily provide symptomatic relief without altering disease progression, highlighting the need for novel therapeutic strategies beyond traditional drug therapies [2]. Group 1: Gut-Brain Axis and Parkinson's Disease - The gut-brain axis has emerged as a critical component in the pathogenesis of Parkinson's disease, with evidence suggesting that misfolded α-synuclein may originate from the gut and ascend to the brain via the vagus nerve [3]. - Gastrointestinal symptoms, particularly constipation, often precede motor symptoms in Parkinson's patients, indicating a potential prodromal phase of neurodegeneration [3]. - Patients with Parkinson's disease frequently exhibit gut barrier dysfunction, inflammation, and dysbiosis, supporting the notion that gut microbiota imbalance may promote the onset and progression of the disease [3]. Group 2: Fecal Microbiota Transplantation (FMT) Research - Early clinical studies have shown that fecal microbiota transplantation (FMT) can alleviate constipation symptoms in Parkinson's patients and, in some cases, improve motor symptoms, although results from randomized controlled trials have been inconsistent due to variations in administration routes, microbial preparation methods, and patient selection [3][6]. - A recent randomized, double-blind, placebo-controlled phase 2 trial demonstrated that repeated donor fecal transplantation (dFMT) is safe and well-tolerated in drug-naïve Parkinson's patients, showing clinically meaningful improvements in motor and gastrointestinal symptoms [4][6]. Group 3: Clinical Trial Results - In the trial, 72 patients were randomly assigned to receive either dFMT or autologous fecal microbiota transplantation (aFMT), with 66 completing the study. Results indicated significant improvement in motor symptoms for the dFMT group, with a mean change in the Unified Parkinson's Disease Rating Scale III of -3.8 compared to +0.1 for aFMT [6]. - The severity of constipation also decreased more significantly in the dFMT group (-6.5 vs -0.7), indicating a robust therapeutic effect [6]. - Analysis of gut microbiota showed that dFMT patients had a microbiome composition more similar to that of the donors, with a notable reduction in Escherichia-Shigella, correlating with decreased colonic α-synuclein aggregation [7]. Group 4: Safety and Mechanistic Insights - Biochemical analyses revealed increased levels of dopamine and 3,4-dihydroxyphenylacetic acid in feces, alongside enhanced intestinal epithelial barrier integrity and increased expression of E-cadherin [7]. - All adverse events reported were mild and self-limiting, with no serious treatment-related events observed, supporting the safety profile of dFMT in this patient population [7].