Positive effect of an electrolyzed reduced water on gut permeability, fecal microbiota and liver in an animal model of Parkinson’s disease

There is growing awareness within the scientific community of the strong connection between the inflammation in the intestine and the pathogenesis of Parkinson’s disease (PD). In previous studies we developed a PD animal model exposing pup rats to permethrin (PERM) pesticide. Here, we intended to explore whether in our animal model there were changes in gut permeability, fecal microbiota and hepatic injury. Moreover, we tested if the co-treatment with an electrolyzed reduced (ERW) was effective to protect against alterations induced by PERM. Rats (from postnatal day 6 to 21) were gavaged daily with PERM, PERM+ERW or vehicle and gut, liver and feces were analyzed in 2-months-old rats. Increased gut permeability, measured by FITC-dextran assay, was detected in PERM group compared to control and PERM+ERW groups. In duodenum and ileum, concentration of occludin was higher in control group than those measured in PERM group, whereas only in duodenum ZO-1 was higher in control than those measured in PERM and PERM+ERW groups. Number of inflammatory focis and neutrophils as well as iNOS protein levels were higher in livers of PERM-treated rats than in those of PERM+ERW and control rats. Fecal microbiota analysis revealed that Lachnospira was less abundant and Defluviitaleaceae more abundant in the PERM group, whereas the co-treatment with ERW was protective against PERM treatment since the abundances in Lachnospira and Defluviitaleaceae were similar to those in the control group. Higher abundances of butyrate- producing bacteria such as Blautia, U.m. of Lachnospiraceae family, U.m. of Ruminococcaceae family, Papillibacter, Roseburia, Intestinimonas, Shuttleworthia together with higher butyric acid levels were detected in PERM+ERW group compared to the other groups. In conclusion, the PD animal model showed increased intestinal permeability together with hepatic inflammation correlated with altered gut microbiota. The positive effects of ERW co-treatment observed in gut, liver and brain of rats were linked to changes on gut microbiota.

科学界日益认识到肠道炎症与帕金森病（Parkinson’s disease, PD）发病机制之间存在密切关联。在既往研究中，我们构建了幼鼠暴露于氯菊酯（permethrin, PERM）农药的PD动物模型。本研究旨在探究该动物模型中是否存在肠道通透性、粪便菌群及肝损伤的改变；此外，我们还测试了电解还原水（electrolyzed reduced water, ERW）联合治疗能否有效抵御PERM诱导的机体异常变化。将出生后第6天至第21天的大鼠每日经口灌服PERM、PERM+ERW或溶剂对照，并在大鼠2月龄时对其肠道、肝脏及粪便样本进行分析。通过异硫氰酸荧光素-葡聚糖（FITC-dextran）实验检测发现，与对照组及PERM+ERW组相比，PERM组大鼠的肠道通透性显著升高。在十二指肠与回肠中，对照组的闭合蛋白（occludin）浓度高于PERM组；而仅在十二指肠中，对照组的紧密连接蛋白-1（ZO-1）浓度高于PERM组与PERM+ERW组。PERM处理组大鼠肝脏中的炎症病灶数量、中性粒细胞计数及诱导型一氧化氮合酶（iNOS）蛋白水平均高于PERM+ERW组与对照组。粪便菌群分析结果显示，PERM组大鼠的毛螺菌属（Lachnospira）丰度降低，脱氟杆菌科（Defluviitaleaceae）丰度升高；而ERW联合治疗可对PERM处理起到保护作用，此时毛螺菌属与脱氟杆菌科的丰度与对照组相近。与其余两组相比，PERM+ERW组的产丁酸菌（如布劳特氏菌属（Blautia）、毛螺菌科未分类菌、瘤胃球菌科未分类菌、乳头菌属（Papillibacter）、罗斯氏菌属（Roseburia）、肠单胞菌属（Intestinimonas）、舒特沃氏菌属（Shuttleworthia））丰度更高，且丁酸水平也显著升高。综上，本研究中的PD动物模型出现了肠道通透性升高及肝脏炎症，且该改变与肠道菌群紊乱相关。ERW联合治疗在大鼠肠道、肝脏及脑组织中展现的保护作用，与其对肠道菌群的调控密切相关。