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.