College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, 300457, P. R. China.
College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, P. R. China.
Mol Nutr Food Res. 2022 Oct;66(19):e2200265. doi: 10.1002/mnfr.202200265. Epub 2022 Aug 31.
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, is demonstrated to improve the cognitive deficits and anxiety-like behaviors in the d-galactose/AlCl induced AD rats, and attenuate the neuronal degeneration and Aβ accumulation in the brain. Moreover, the study finds MA2 could alleviate the intestinal mucosal impairments, and impedes the activation of microglia and neuroinflammation through TLR4/MYD88/NLRP3 signaling pathway. 16S rRNA sequencing and metabolomic analysis indicate that MA2 reshapes the gut microbiota structure and composition, and remarkably modulates the glycometabolism. In that case, the exopolysaccharides (EPS) that derived from MA2 is 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 to develop new intervention and therapeutic strategy on AD using probiotics and their metabolites.
通过益生菌来调节肠道微生物群是合理预防和治疗阿尔茨海默病（AD）的有效策略。然而，目前针对 AD 的保护缺乏知名的益生菌种类，其涉及的机制尚未得到明确解释。
本文证明，从传统中国藏式开菲尔粒中分离出的功能性益生菌植物乳杆菌 MA2（MA2）可改善半乳糖/AlCl 诱导的 AD 大鼠的认知缺陷和焦虑样行为，并减轻大脑中的神经元变性和 Aβ 积累。此外，研究发现 MA2 可以减轻肠道黏膜损伤，并通过 TLR4/MYD88/NLRP3 信号通路抑制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，并显著调节了糖代谢。在这种情况下，进一步证明 MA2 的胞外多糖（EPS）对 Aβ42 聚集和淀粉样蛋白诱导的细胞毒性具有抑制作用。
MA2 或 MA2 EPS 可作为功能性食品和营养补充剂，用于调节 AD 中的肠道微生物群和代谢紊乱。这项研究对于开发使用益生菌及其代谢物治疗 AD 的新干预和治疗策略具有重要意义。
