Investigation of the Mitigating Mechanism of Bifidobacterium longum 300 in d-Galactose-Induced Cognitive Impairment in Mice

People’s aging is accompanied by cognitive impairment, especially the decline in learning and memory ability. Probiotics have potential health-promoting functions in this regard. In this study, the function of Bifidobacterium longum 300 (BL300) in reducing cognitive impairment of mice induced via d-galactose was evaluated, and the mitigating mechanism of this function was deeply researched. Treatment with BL300 significantly enhanced the nesting ability of the mice, increased their time spent in the target quadrant of the water maze, and reduced the number of errors in passive avoidance tests (PAT). Notably, BL300 treatment facilitated recovery in the gut microbiota composition by increasing beneficial microbial populations (e.g., Lactobacillus) and decreasing pathogenic bacteria. Importantly, compared to mice treated with d-galactose, the indices of inflammation and acetylcholinesterase levels in the hippocampus and serum were decreased, along with a downregulation of pro-inflammatory cytokines in the brain (such as TNF-α and IL-6) when they were fed with BL300. Furthermore, the administration of BL300 resulted in an increase in the populations of BDNF+ and NeuN+ cells in the hippocampus and reduced intestinal permeability. Therefore, this study provides compelling evidence for the BL300 can reduce cognitive decline, and BL300 would be regarded as a potential probiotic for alleviating cognitive impairment.