Modulation of the Gut Microbiota and Glycometabolism by a Probiotic to Alleviate Amyloid Accumulation and Cognitive Impairments in AD Rats

Scope 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. Methods and results 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 3 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. Conclusion 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.