Synergistic protective effects of probiotics Lactiplantibacillus plantarum S58 and prebiotics Qingke β-glucan on dextran sulfate sodium-induced cognitive deficits in colitis mice: A study of microbial-gut-brain axis modulation

Probiotics and prebiotics have significant potential for mitigating colitis; however, the synergistic effect of their combination in alleviating colitis-associated cognitive deficits remains to be elucidated. This study aimed to reveal the synergistic protective effects and mechanisms of the prebiotic Qingke beta-glucan (beta-G) and the beta-G- utilizing probiotic Lactiplantibacillus plantarum S58 (LP.S58) on cognitive deficits induced by dextrose sodium sulfate (DSS)-induced colitis in a mouse model. The results demonstrated that the combination of LP.S58 and beta-G (LP.S58+beta-G) more effectively ameliorated pathological changes and memory and learning behavioral abnormalities in colitis mice than LP.S58 and beta-G administration. Concurrently, LP.S58+beta-G attenuated hippocampal synaptic damage and neuronal apoptosis in colitis mice by inhibiting pro-inflammatory cytokines and excessive neuroglial cell over-activation while also counteracting the degradation of synaptic proteins. Furthermore, LP. S58+beta-G effectively ameliorated intestinal immune dysfunction by regulating inflammatory mediators and enhancing the expression of tight-junction proteins. Notably, LP.S58+beta-G significantly reshaped the gut microbiome and reduced pro-inflammatory bacteria, such as Clostridium, Streptococcus, and Romboutsia, in colitis mice. Correlation analysis further indicated that the LP.S58+beta-G-inhibited lipopolysaccharide (LPS)/NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3)/Caspase-1/ASC/IL-1 beta signaling pathway plays a key role in alleviating cognitive deficits. Overall, these findings offer novel insights into the synergistic protection of probiotics and prebiotics against colitis-associated cognitive deficits by modulating the microbe-gut-brain axis.