Bifidobacterium animalis subsp. animalis derived-vesicles alleviate cognitive impairment in mice via modulating gut microbiota metabolism and 5-HT/BDNF pathway

Hippocampal neuroinflammation (HNF) causes gut microbial abnormalities to aggravate cognitive impairment. Bifidobacterium could alleviate HNF to improve cognitive impairment. However, the role of Bifidobacterium derived-membrane vesicles (MV) reshape gut microbiota in connection with cognitive impairment is remains insufficiently. This study employed LPS-induced mice to determine the Bifidobacterium animalis subsp. animalis (BL) 99-MV on preventing cognitive impairment and the relevant mechanisms involved. Phenotypic results showed that BL99-MV supplementation inhibited IL-33, IL-1b and TNF-levels, increased brain-derived neurotrophic factor (BDNF) level, reduced Ab, Tau, P-Tau (Ser404) and GSK-3b expression and improved cognitive impairment in mice. The metagenomic analysis proved that BL99-MV supplementation restored the dysbiosis of the gut microbiota, increased the relative abundance of Clostridium and Oscillibacter. The metabolomics showed that BL99-MV increased the hippocampal BDNF expression, which enhanced the conversion 5-hydroxytryptophan (5-HTP) to 5-hydroxytryptamine (5-HT) to improve learning. More importantly, the level of 5-HT exhibited a positive correlation with the abundances of Clostridium and Oscillibacter. Our findings illuminate that a novel and promising BL99-MV to improve LPS-induced HNF and accompanying gut disorder, and provide options for preventing gut-brain axis- related cognitive function.