Therapeutic potential of Lacticaseibacillus rhamnosus grx10 and its derived postbiotic through gut microbiota and MAPK/MLCK/MLC pathway‐mediated intestinal barrier repairment in ulcerative colitis

Abstract Lacticaseibacillus rhamnosus grx10 (grx10) has shown promising potential in promoting intestinal health as predicted by genomic and metabolomic analyses. Given the increasing prevalence of ulcerative colitis (UC) and the limitations of existing treatments, exploring alternative therapeutic strategies is essential. This study explored the therapeutic effects and underlying mechanisms of grx10 and its derived postbiotic (P‐grx10) in a mouse model of dextran sulfate sodium (DSS)‐induced chronic UC. The intervention with grx10 and P‐grx10 significantly alleviated clinical symptoms and improved biochemical markers in UC mice. These effects included reducing the disease activity index (DAI), improving colon length and histopathological damage, decreasing the secretion of inflammatory cytokines, and preventing the reduction of antioxidant enzymes. Additionally, grx10 and P‐grx10 downregulated key proteins in the Mitogen‐Activated Protein Kinase (MAPK)/myosin light chain kinase (MLCK)/myosin light chain (MLC) pathway, prevented the dissociation of tight junction (TJ) proteins and E‐cadherin, reduced intestinal permeability, and restored the integrity of the intestinal barrier. Furthermore, both grx10 and P‐grx10 modulated the composition and abundance of gut microbiota, helping to maintain intestinal microbiome homeostasis. In conclusion, this study provided evidence regarding the role of grx10 and P‐grx10 in alleviating intestinal barrier dysfunction associated with UC and restoring gut microbiota balance. Notably, P‐grx10 exhibited higher anti‐inflammatory activity and better restoration of intestinal barrier function, whereas the live probiotic grx10 showed a stronger regulatory effect on the gut microbiota. These findings suggest that grx10 and P‐grx10 could serve as promising nutritional adjunct therapies for UC, providing novel insights into the distinct roles of probiotic and its derived postbiotic in UC treatment.