Nutrigenomica come strategia di prevenzione nella neurodegenerazione

Permethrin (PERM) is a pesticide belonging to the pyrethroid family that has been used to induce Parkinson’s disease (PD) in rats [1]. Although PD is considered as a movement disorder, it has long been recognized that non-motor symptoms such as gastrointestinal dysfunctions precede the classical disease features. New evidence suggests that microbial pathogens and associated immune/inflammatory responses might start the detrimental process in the gut and spread via the vagal nerve to the CNS. Food-based therapies might then have an impact on PD pathology by altering microbiota composition and/or improving non-motor as well as motor symptoms in PD. The aim of our study was to evaluate the effect of a functional drinking water or electrolyzed reducing water (ERW) on the intestinal permeability, fecal butyrate content and microbiota in an animal model of PD. The ERW is a hydrogen-rich water with antioxidant activity due to its negative oxidation reduction potential (ORP = - 400 mV). All experiments on animals were approved by the Italian Ministry of Health (n. 393/2016-PR). Male rat pups born in our laboratory were assigned to three treatment groups (n=18 PD rats, n=16 controls and n=18 PD+ERW-treated rats). The first group was treated once daily by gavage with PERM (34 mg/4 mL/kg body weight) from postnatal day (PND) 6 to PND 21, whereas the second group (control) was treated with the vehicle (corn oil 4 mL/kg body weight) on a similar schedule. A third group was gavaged once a day with PERM (34 mg/4 mL/kg body weight) and co-treated twice a day (early morning and late afternoon) with ERW (10 mL/kg body weight) from PND 6 to PND 21. ERW produced by a water ionizer (Chanson Revolution 9 plates, Taiwan), is a functional drinking water with pH=10, able to reduce by means of its hydrogen concentration (400 ppm). Before administration, the alkaline water was buffered with citric acid at a pH=7.5. On PND 60, animals were submitted to analysis. The in vivo intestinal permeability was tested by oral administration of a fluorescent marker FITC-dextran and measurement of its concentration in the plasma. The PD group revealed a significant increased intestinal permeability compared to the control group, whereas no difference was observed between PD+ERW group and control one (P<0.05). These results show that the treatment with PERM pesticide disrupts the intestinal barrier integrity and the co-treatment with ERW is able to protect against it. Since the intestinal barrier acts as a shield which can be modified by the gut microbiota and its metabolites such as the short chain fatty acids (SCFAs), microbiota composition and SCFA content were analyzed by 16S rRNA gene sequencing and gas-chromatography, respectively. The results showed an increase of butyrate content in the feces of PD animals co-treated with ERW together with an increased butyric acid producing bacteria (especially Roseburia and Lachnospira species) compared to the others groups. This study demonstrates that the ERW, a functional drinking water, could create a gut environment favourable for the fermentation process producing butyric acid that serves as primary energy source for colonocytes. Food-base therapy such as ERW drinking or/and a diet rich in natural sources of butyrate is a highly appealing approach that, if validated, may be used in conjunction with traditional pharmacological treatments to improve outcomes in patients with brain disorders. Reference [1] Nasuti C, Brunori G, Eusepi P, Marinelli L, Ciccocioppo R, Gabbianelli R. Early life exposure to permethrin: a progressive animal model of Parkinson's disease. J Pharmacol Toxicol Methods. 2017; 83: 80-86.