Abstract
Bifidobacterium animalis subsp. lactis GCL2505 (GCL2505), commercially known as the "BifiX" strain in Japan, reaches the intestine alive, proliferates after a single intake, and is associated with several positive health effects. A randomized, double-blind, placebo-controlled, parallel-group clinical trial of this probiotic strain in combination with inulin (a prebiotic) reported an improvement of cognitive function in the elderly. In the present study, a follow-up analysis was performed to elucidate the underlying mechanism, using a multi-omics approach that integrated a high-throughput assay of blood inflammatory markers and metagenomic analysis of the fecal bacterial composition. After probiotic and prebiotic administration, short-chain fatty acid producers such as Faecalibacterium and Bifidobacterium were increased in the gut. Moreover, in the subgroup with greater improvement in cognitive function scores, the levels of inflammatory markers were decreased. Subgroup analysis revealed that the improvement of cognitive function was associated with a reduction of inflammation and an increase of Faecalibacterium. These results suggest that GCL2505 and inulin can improve cognitive function by alleviating inflammation via an increase of short-chain fatty acid-producing bacteria, which appears to elevate levels of short-chain fatty acids, particularly acetate and butyrate, in the gut. The present results contribute to a deeper comprehension of the gut-brain axis and propose new avenues for potential therapeutic intervention in cognitive disorders.