1.0320 Postbiotics Ameliorate Dextran Sodium Sulfate-Induced Colonic Inflammation and Oxidative Stress by Regulating the Intestinal Barrier and Gut Microbiota.

Probiotics are increasingly being used as an adjunctive therapy for ulcerative colitis. However, some safety issues have been found in the clinical use of probiotics. Postbiotics have attracted much attention due to their storage stability, safety, and potential functions, but the dose required to exert a significant protective effect is unknown. Therefore, this study evaluated the potential mechanisms of different doses (200, 400, 600 mg/kg) of 1.0320 postbiotics (1.0320P) in alleviating dextran sodium sulfate (DSS)-induced colitis. The study revealed that 1.0320P could mitigate DSS-induced colitis with signs of reductions in the disease activity index, amelioration of colon tissue damage, decreased secretion of proinflammatory cytokines, reduced oxidative stress levels, and lower bone marrow peroxidase activity. Furthermore, high dose of 1.0320P could upregulated the expression of key proteins in the Nrf2/ARE pathway (NQO1, Nrf2, and HO-1) and downregulated the expression of key proteins in the TLR4/NF-κB signaling pathway (TLR4, MyD88, and NF-κB p65). In addition, high dose of 1.0320P could upregulate the expression of tight junction (TJ) proteins including ZO-1, Occludin, and Claudin-1, contributing to the restoration of the intestinal mucosal barrier function. Additionally, 1.0320P was found to effectively correct imbalances in the intestinal microbiota and enhance the synthesis of short-chain fatty acids (SCFAs), thereby regulating homeostasis in the intestinal internal environment. Overall, our findings suggest that postbiotics could ameliorate colonic inflammation while being somewhat dose-dependent. This study provides new insights into postbiotics as a next-generation biotherapeutic agent for the treatment of ulcerative colitis and even other diseases.