Bifidobacterium animalis subspecies lactic 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. While Bifidobacterium has been shown to alleviate HNF and improve cognitive function, the role of Bifidobacterium-derived membrane vesicles (MV) in reshaping gut microbiota and their connection to cognitive impairment remains poorly understood. This study employed LPS-induced mice to determine the Bifidobacterium animalis subsp. lactis (BL) 99-MV on preventing cognitive impairment and the relevant mechanisms involved. Phenotypic results showed that BL99-MV supplementation inhibited IL-33, IL-1β and TNF-α level, increased brain-derived neurotrophic factor (BDNF) level, reduced Aβ, Tau, P-Tau (Ser404) and GSK-3β expression and improved cognitive impairment in mice. Metagenomic analysis revealed that BL99-MV supplementation restored gut microbiota dysbiosis, increased the relative abundance of Clostridium and Oscillibacter. Metagenomic analysis revealed 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.