【作者】 贾龙刚； 王远望； 王德华； 吕厚娇； 耿伟涛； 王金菊； 王艳萍；

【Author】 Jia Longgang;Wang Yuanwang;Wang Dehua;Lv Houjiao;Geng Weitao;Wang Jinju;Wang Yanping;College of Food Science and Engineering,Tianjin University of Science & Technology;

【机构】 天津科技大学食品科学与工程学院；

【摘要】 益生菌调节肠道微生态是预防和改善阿尔茨海默病（Alzheimer’s disease,AD）的有效策略。然而,目前已报道的具有预防AD功能的益生菌种类较少,且作用机制尚未明确解析。植物乳杆菌MA2 （MA2）是一种从中国传统藏族开菲尔粒中分离出来的功能性益生菌,本研究发现MA2可改善D-半乳糖/AlCl₃诱导的AD大鼠的认知缺陷和焦虑样行为,并减轻神经元变性和淀粉样蛋白（Aβ）在大脑中沉积。此外,我们发现MA2可通过调节TLR4/MYD88/NLRP3信号通路来缓解肠黏膜损伤,并阻碍小胶质细胞的激活和神经炎症。16S rRNA测序和代谢组学分析表明,MA2重塑了肠道微生物群的结构和组成,并对糖代谢的调节作用最为明显。进一步地,我们证明了MA2胞外多糖（EPS）对Aβ42聚集及其诱导的细胞毒性具有显著的抑制作用。因此,MA2及其EPS可用于调节AD肠道微生物菌群和代谢紊乱的功能性食品和营养补充剂。同时,本研究对于利用益生菌及其代谢产物,开发新型干预和改善AD的策略具有重要意义和应用价值。更多还原

【Abstract】 Regulating the gut microecology by probiotics is an efficient strategy to rational prevention and treatment of Alzheimer’s disease(AD).However,there is currently a lack of well-known probiotic species in the protection against AD,and the involved mechanism has not been clearly interpreted.Herein,Lactobacillus plantarum MA2(MA2),a functional probiotic isolated from traditional Chinese Tibetan kefir grains,was demonstrated to improve the cognitive deficits and anxiety-like behaviors in the D-galactose/AlC13 induced AD rats,and attenuate the neuronal degeneration and Aβ accumulation in the brain.Moreover,we found MA2 could alleviate the intestinal mucosal impairments,and impede the activation of microglia and neuroinflammation through TLR4/MYD88/NLRP3 signaling pathway.16 S rRNA sequencing and metabolomic analysis indicated that MA2 reshaped the gut microbiota structure and composition,and remarkably modulated the glycometabolism.In that case,the EPS(exopolysaccharides) that derived from MA2 was furtherly proved with inhibitory effects on the Aβ42 aggregation and amyloid-induced cytotoxicity.MA2 or MA2 EPS may be used as functional food and nutritional supplement for regulating the gut microbiota and metabolism disorders in AD.This study is of great significance and application value for the use of probiotics and their metabolites to develop novel strategies to intervene and improve AD.更多还原