<i>Lactiplantibacillus plantarum</i> HY7715 Attenuates Oxidative Stress-Induced Neurobiological Aging-Related Changes by Modulating Senescence-Associated Markers and Gut Microbiota.

External stressors can accelerate biological aging-related processes by promoting oxidative stress and senescence(definition)-associated molecular alterations in the brain. This study investigated the potential of <i>Lactiplantibacillus plantarum</i> HY7715 to attenuate oxidative stress-induced neurobiological aging-related changes using H₂O₂-induced HT22 hippocampal cells and a restraint-stressed mouse model. In HT22 cells, HY7715 reduced reactive oxygen species accumulation, decreased 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, and lowered the proportion of senescence-associated β-galactosidase-positive cells. These effects were accompanied by suppression of p53/p21 signaling and restoration of <i>Tert</i> expression. In restraint-stressed mice, HY7715 reduced the number of p21-positive cells in the hippocampus, significantly lowered <i>p53</i> expression, restored <i>Tert</i> expression, reduced <i>Il-6</i> expression, and improved antioxidant-related gene expression, including <i>Gpx1</i> and <i>Sod1</i>. Microbiome analysis showed that HY7715 reshaped the stress-altered gut microbiota toward a <i>Lactobacillus</i>-enriched profile and reduced the abundance of <i>Lachnospiraceae, Acetatifactor, Desulfovibrio</i>, and <i>Oscillibacter</i>. Collectively, these findings suggest that HY7715 may attenuate oxidative stress-induced neurobiological aging-related changes by modulating senescence-associated molecular markers and stress-altered gut microbiota, highlighting its potential as a candidate for supporting healthy brain aging.