Live and Heat-Killed Lactiplantibacillus plantarum HY7715 Attenuate D-Galactose-Induced Aging-Related Brain Changes and Blood-Brain Barrier Disruption with Gut Microbiota Modulation in Mice.

Aging is associated with changes in systemic homeostasis, intestinal barrier integrity, and brain function. This study investigated the effects of Lactiplantibacillus plantarum HY7715 on aging-related alterations in a D-galactose-induced accelerated aging mouse model. Male C57BL/6J mice were administered D-galactose for 8 weeks and orally treated with live or heat-killed HY7715. D-galactose increased circulating advanced glycation end products (AGEs), blood-brain barrier (BBB) permeability, hippocampal inflammation, and aging-related molecular changes, while impairing cortical and colonic tight junction-associated markers. Both live and heat-killed HY7715 reduced serum AGE levels, Evans blue leakage, and hippocampal inflammatory responses, while restoring CLDN5 immunoreactivity, tight junction-associated gene expression, and antioxidant-related gene expression. HY7715 also attenuated senescence- and apoptosis-related changes in the hippocampus and colonic tight junction- and inflammation-related gene expression changes. Gut microbiota analysis showed taxon-specific changes following HY7715 treatment, including significant increases in Bifidobacterium in both HY7715-treated groups, whereas live HY7715 was associated with significant changes in microbial community structure. Several microbial taxa were correlated with serum AGEs, BBB permeability, and neuroinflammation-related parameters. Together, these results show that both live and heat-killed HY7715 attenuated multiple aging-related changes in the D-galactose-induced accelerated aging model, accompanied by changes in gut microbiota composition.