Rationale and current status of fecal microbiota transplantations for Parkinson's disease

Treating a neurological disorder through the gut may seem counterintuitive, yet multiple lines of evidence highlight the gut's important role in Parkinson's disease (PD). Prodromal gastrointestinal symptoms, the presence of aggregated α-synuclein in enteric neurons, increased intestinal inflammation, and impaired epithelial barrier integrity all point to gut-level involvement in PD pathophysiology. The gut microbiome, markedly altered in individuals with PD, may be a key driver of these changes. Fecal microbiota transplantation (FMT) is currently the most effective strategy for achieving broad and durable modifications of gut microbiota composition. However, FMT is a complex, multi-step procedure requiring stringent methodological control. Modulating gut bacteria has demonstrated therapeutic potential in preclinical models of PD, and recent clinical trials have begun evaluating FMT in patients, although outcomes have been variable. In this review, we examine potential explanations for these divergent results, with a particular focus on methodological differences across trials. We also outline future directions for optimizing FMT study design in PD and discuss how these insights may guide the development of next-generation microbiota-targeted therapies.