Ameliorative Effects and Mechanisms of <italic>Pediococcus acidilactici</italic> I1-2 from the Qinghai-Tibet Plateau on Chronic Stress-induced Depressive Behavior

Objective: This study aimed to investigate the ameliorative effects and underlying mechanisms of Pediococcus acidilactici I1-2, a strain isolated from traditional fermented foods of the Qinghai-Tibet Plateau, on depressive behavior induced by chronic stress through in vivo experiments. Methods: C57BL/6J mice were randomly assigned to three groups: control, model, and P. acidilactici I1-2 intervention groups. A depression model was established by subjecting the mice to six weeks of chronic unpredictable mild stress (CUMS). Depressive and anxiety-like behaviors were assessed using the open field test, elevated plus maze, tail suspension test, and sucrose preference test. Cortical levels of serotonin (5-HT) and dopamine (DA) were quantified via high-performance liquid chromatography (HPLC). Additionally, levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) in the hippocampus and serum were measured, alongside mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-22) in the hippocampus. Microglial activation in the brain was evaluated using IBA-1 immunofluorescence staining. Results: Intervention with P. acidilactici I1-2 significantly increased the time spent and distance traveled in the central area of the open field (PPPPPPPP. acidilactici I1-2 significantly downregulated the gene expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 (PIL-22 (PPPediococcus acidilactici I1-2, as a foodborne probiotic, significantly ameliorates depressive behavior induced by chronic stress. These findings provide a foundation for the development and application of probiotics in functional foods targeting brain health.