Probiotic novel strain Lactobacillus reuteri MRD01 alleviates dextran sulfate sodium-induced colitis in male mice by promoting intestinal barrier integrity.

Abstract

Intestinal barrier dysfunction contributes to the progression of inflammatory bowel disease (IBD), yet current therapies provide limited symptom relief, are associated with substantial long-term adverse effects, and exhibit high recurrence rates. Lactobacillus reuteri (L. reuteri), a probiotic with strong colonisation capacity in the gastrointestinal tract, produces metabolites that regulate intestinal microecology. This study explored the therapeutic efficacy and underlying mechanisms of a newly isolated strain, L. reuteri MRD01, in a dextran sodium sulfate (DSS)-induced colitis model. Our results showed that L. reuteri MRD01 effectively mitigated DSS-induced colitis in mice. Administration of MRD01 alleviated body weight loss and partially recovered body weight, attenuated colon shortening, and significantly reduced the disease activity index (DAI), spleen index, and histopathological damage scores. The strain increased MUC2 expression and goblet cell numbers, possibly enhancing mucin secretion and reinforcing the intestinal mucosal barrier. Additionally, MRD01 improved epithelial integrity by upregulating zonula occludens-1 (ZO-1) and occludin expression, and reducing the leakage of fluorescein isothiocyanate-dextran (FITC-dextran; FD4). The strain modulated the inflammatory response by downregulating interleukin (IL)-1β, IL-6, and tumour necrosis factor-α (TNF-α), whereas enhancing IL-10 expression. This cytokine modulation rebalanced macrophage polarisation and inhibited the Toll-like receptor 4 (TLR4)-nuclear factor-κB (NF-κB)-NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway, thereby attenuating systemic inflammation. Mechanistically, L. reuteri MRD01 altered the gut microbial composition, contributing to the restoration of intestinal homeostasis. These results substantially revealed that L. reuteri MRD01 alleviated colitis by synergistically enhancing mucosal protection, epithelial integrity, immune homeostasis, and microbial balance. These findings support its therapeutic potential as a probiotic-based strategy for IBD management.