The gut-brain axis serves as a vital communication pathway through which gut microbiota modulates central nervous system function. Chronic stress disrupts this balance, leading to gut dysbiosis, neuroinflammation, and cognitive decline. While probiotics have been widely investigated, the therapeutic properties of their non-viable metabolites, postbiotics, are less understood. This study examined the neurocognitive effects of postbiotics derived from Lactobacillus rhamnosus and Bifidobacterium longum in a mouse model of chronic variable stress (CVS). Male BALB/c mice underwent a four-week CVS protocol, followed by eight weeks of oral postbiotic administration (10⁹ CFU/mL bacterial supernatant) from individual or mixed strains. Cognitive performance was evaluated using the Morris Water Maze (MWM), Novel Object Recognition (NOR), and Shuttle Box tests, while hippocampal expression of AKT and Arc, genes linked to learning and memory, was analyzed by qRT-PCR. CVS markedly impaired performance across all cognitive tests. Postbiotic supplementation significantly reversed these deficits, with Bifidobacterium longum postbiotics exerting the most robust effects. Treated mice showed reduced escape latency and shorter platform distance in the MWM, improved discrimination in the NOR test, and increased latency to the dark compartment in the Shuttle Box, indicating enhanced spatial, recognition, and inhibitory memory. These behavioral improvements correlated with upregulated hippocampal AKT and Arc expression, suggesting strengthened synaptic signaling. Overall, postbiotic treatment, particularly from Bifidobacterium longum, effectively mitigated stress-induced cognitive dysfunction, highlighting postbiotics as promising therapeutic agents for stress-related and neurodegenerative cognitive impairments.
Gut-Brain Axis