This 2x2 factorial, randomized, controlled pilot study aims to identify a specific microbiota pattern, which could constitute a biomarker of Parkinson's disease, and to evaluate whether specific pathotypes can be associated with different stages of the disease; furthermore, the investigators are committed to evaluating how and to what extent the changes induced by a personalized nutritional intervention combined with physical exercise affect the symptoms and quality of life of patients.
The study will last 60 months, and the following activities are planned: * Study presentation, selection and enrollment of patients; * Evaluation of patients' health and nutritional status, including collection of physiological, pathological, and pharmacological history; * Randomization of patients into four groups; * Sample collection and storage; * Microbiome analysis; * Evaluation of motor and non-motor symptoms using clinical tests and rating scales at baseline (T0), at six months (T1) after treatment initiation, and at three and six months post-intervention (FU1 and FU2, respectively).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
80
Participants will follow a personalized diet plan over 24 weeks, based on the guidelines of the Mediterranean diet and defined according to their needs and the state of the disease; no food category will be excluded a priori. Individualized nutritional counseling and support materials (weekly meal plans, sample recipes, portion guides) will be provided by a qualified nutritionist. Adherence to the Mediterranean diet will be monitored periodically. Participants will maintain their usual diet during a pre-baseline period of at least 4 weeks, then switch to the Mediterranean plan under the supervision of a nutritionist.
Participants will perform exercise, over 24 weeks, according to WHO recommendations for adults, including those aged ≥ 64 years, to achieve at least 150-300 minutes of moderate-intensity aerobic physical activity, or at least 75-100 minutes of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate and vigorous activity during the week. The WHO 2020 also recommend moderate-intensity or greater muscle-strengthening exercises involving alla major muscle groups for 2 or more days per week. Adherence will be monitored during in-person sessions and through wearable devices for activity tracking.
Alpha Diversity of the fecal microbiota.
Changes in fecal microbiota alpha diversity, a measure of the richness and evenness of microbial species within a sample, will be assessed.
Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Beta Diversity of the fecal microbiota
Changes in fecal microbiota beta diversity, refers to the degree of difference in microbial community composition between different fecal samples, will be assessed.
Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Enterobacteriaceae species abundance across Parkinson's disease stage
Changes in fecal microbial composition will be assessed. Specifically, we will measure the relative abundance of Enterobacteriaceae species and pathotypes across different stages of Parkinson's disease.
Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Fecal Microbial relative quantification
Changes in relative quantification
Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Intestinal Inflammation
Changes in fecal calprotectin (a valid and non-invasive marker of mucosal inflammation) will be assessed using enzyme-linked immunosorbent assay (ELISA).
Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Intestinal Permeability
Changes in fecal zonulin will be assessed using enzyme-linked immunosorbent assay (ELISA). The unit for measuring zonulin in stool samples is nanograms per milliliter (ng/mL). The Protein Zonulin is a very important indicator for leaky gut.
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Participants will continue their usual medical management for early Parkinson's disease according to current clinical guidelines, without any additional dietary or exercise interventions provided by the study, and will be monitored through standard follow-up visits but will not receive any study-specific dietary or physical activity programs.
Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Changes in extracellular vesicle concentration (particles/mL) in saliva and plasma will be assessed.
To evaluate the effect of the combined diet and physical activity intervention on extracellular vesicles (EVs), EVs will be isolated from saliva and plasma by serial ultracentrifugation and size-exclusion chromatography. EV concentration and size distribution will be determined by nanoparticle tracking analysis (NTA).
Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)
Changes in protein marker expression in saliva and plasma.
Extracellular Vesicles (EVs)-associated proteins (CD63, CD9, α-synuclein, BDNF, L1CAM, and CD56) will be quantified by dot blot and confirmed by fluorescent NTA and/or cytofluorimetric analysis.
Time frame: Baseline (Week 0); End of intervention (Week 24); First Follow-up (Week 36); Second Follow-up (Week 48)