Opposite regulatory effects of Blautia massiliensis and Blautia faecis on cognitive function, microglia and metabolite acetic acid in mice.

Cognitive impairment is a significant health problem worldwide, closely associated with the status of gut microbiota. Our recent research has revealed the Blautia faecis and Blautia massiliensis exhibit opposing associations with cognitive function in children with Down syndrome clinically characterized by cognitive dysfunction. However, the role and mechanisms of Blautia faecis and Blautia massiliensis in cognitive function remain unknown. Therefore, we gavaged C57BL/6 male mice with commercially available Blautia faecis and Blautia massiliensis for 3 weeks and assessed cognitive function using the novel object recognition and Y-maze test. Blautia faecis administration impaired cognitive performance, whereas Blautia massiliensis treatment improved it, with these effects observed predominantly in the absence of antibiotic pretreatment. Furthermore, we observed that administration of Blautia faecis increased the number of microglia, resulting in a twofold increase in cell count relative to WT control. Hippocampal pro-inflammatory cytokines were significantly upregulated in the Blautia faecis group, while Blautia massiliensis suppressed these neuroinflammatory responses. Notably, Blautia massiliensis produces approximately six times more acetate than Blautia faecis. Consequently, our findings indicate that Blautia massiliensis enhances cognitive function whereas Blautia faecis impairs it, and we speculate that differential acetate production may contribute to these opposing effects.