Effects of combined Mediterranean diet and physical activity intervention on the gut microbiome and disease progression in individuals with Parkinson’s disease: study protocol for a multicenter, randomized controlled pilot study (PRIME study)

Background and aims Parkinson’s disease (PD) is a neurodegenerative disorder for which no disease-modifying therapy currently exists, making it crucial to investigate alternative strategies that may slow its progression. The PRIME study will investigate the effects of combined dietary and physical activity interventions- performed in rehabilitative settings with health professional supervision and evaluation, versus single interventions on the gut microbiome in PD. The aim is to identify microbiome profiles – comparing traditional 16s rRNA gene sequencing with the third-generation method – as potential non-invasive, stage specific biomarkers of PD. In addition, the study will assess whether the combined intervention affects disease progression, symptoms, cognitive abilities, and quality of life. Methods Eighty participants with PD will be randomized into four arms: a Mediterranean-diet intervention group; a structured physical-activity group; a combination group receiving both dietary and exercise interventions; a control group receiving standard care only. Conclusion By integrating microbiome characterization with the evaluation of these interventions, the study aims to explore whether intervention-induced changes in the microbiota are associated with clinical improvement in PD, thus paving the way for the design of future non-pharmacological protocols to slow disease progression, mitigate symptom severity, and promote diagnosis. Clinical trial registration https://clinicaltrials.gov/ , identifier NCT07097103.