Our project focuses on comparing the baseline gut microbiota between patients with PD, patients with iRBD and matched healthy controls; to prospectively evaluate the effects of KD compared to a non-KD on motor and non- motor symptoms on patients with PD and iRBD, and to prospectively evaluate the modifications of the gut microbiota in patients with PD and iRBD before and after KD versus a non-KD.

It has been noted that PD patients exhibit both specific alterations in the gut microbiota and signs of intestinal inflammation: it has been hypothesized that misfolding of α-syn may be induced in the enteric nervous system by alterations in the microbiota and then propagate centripetally to the central nervous system via the vagus nerve. It is interesting to note that patients with a prodromal synucleinopathy such as iRBD also show microbiota alterations similar to those observed in PD patients. The ketogenic diet, according to studies conducted at the Clinical Neurology Unit of Udine (DAME), may be a promising treatment for many neurological diseases, including PD.
This type of diet has neuroprotective effects through the production of ketone bodies, which can increase mitochondrial respiration leading to increased ATP production and improve the efficiency of the mitochondrial respiratory chain complex by increasing NADH oxidation and inhibiting the mitochondrial permeability transition.

Patients with PD and with iRBD (Isolated Behavioral Disorder in REM sleep) will be recruited from those followed at the outpatient clinic of the Udine Clinical Neurology Unit; paired healthy controls will be selected from healthy relatives of patients with non-neurodegenerative neurological diseases followed at the outpatient clinic of the Udine Clinical Neurology Unit. Patients will then be randomized to the ketogenic diet (KD) or non-KD, a diet that they will follow for 3 months. The ketogenic diet (KD) is a nutritional treatment consisting of a hypoglucidic, hyperlipidic and normoproteic diet. It induces a state of ketosis, in which the mitochondria of hepatocytes convert lipids into ketone bodies, which represent an alternative and more efficient energy source for neurons compared to glucose. Teach patient, during the first consultation the nutritionist assesses weight, height and BMI and prepares (based on the body composition) a ketogenic diet with a 2:1 ratio in which the amount of fat is equal to twice the amount of carbohydrates and protein. At baseline, a sample of feces and blood will be acquired from all PD and iRBD patients and controls in order to analyze the gut microbiome and markers of inflammation in the three groups.
PD and iRBD patients will then undergo panel of disease-specific questionnaires and scales before and after diet; in addition, changes in body composition (free fat mass, fat mass, BMI) of patients at baseline and after 3 months of diet therapy will be assessed. After the end of the three months of treatment, all patients will follow a washout non-KD diet (Low Glycemic Index Diet) for one month. Then, patients will undergo the same complete clinical evaluation and acquisition of samples of feces and blood. Patients from the KD arm will be assigned a non-KD diet and vice-versa, in a crossover design. Repeat clinical and laboratory evaluations will be performed at months 1 and 3 after the start of the new diet. After treatment with KD and low glycemic index diet, generic nutritional indications will be assigned.