Effects of Lacticaseibacillus rhamnosus KF7-Fermented Milk on Cognitive Function, Gut Microbiota, and Fecal Metabolism in APP/PS1 Mice

Functional fermented dairy products are increasingly investigated as food-based approaches to support health, but their potential relevance to cognitive dysfunction remains unclear. In this study, we evaluated skim milk fermented with Lacticaseibacillus rhamnosus KF7 (KF7-fermented milk) in APP/PS1 transgenic mice. KF7-fermented milk was associated with better cognitive performance and lower amyloid-β plaque burden in APP/PS1 mice. The intervention was also associated with higher whole-blood 5-hydroxytryptamine, lower cerebral glutamate, lower whole-blood expression of pro-inflammatory cytokines, and less pronounced cortical microglial and astrocytic activation. In the intestine, KF7-fermented milk was associated with higher expression of selected barrier-related genes. Microbiome analysis showed differences in gut microbial composition, while fecal metabolomics identified secondary bile acid biosynthesis as the strongest FDR-supported pathway associated with the intervention. Overall, KF7-fermented milk was associated with differences in cognitive, pathological, inflammatory, intestinal, microbial, and metabolic features in APP/PS1 mice. These findings provide preclinical evidence supporting further investigation of KF7-fermented milk as a food-based intervention relevant to gut–brain health.