Synergistic effect of 2′-fucosyllactose and osteopontin on intestinal mucosal immunity injury

Abstract

Previous studies have demonstrated the beneficial effects of 2′-fucosyllactose (2′-FL) and osteopontin (OPN) in modulating intestinal mucosal immunity. Nevertheless, the potential synergistic interactions and underlying mechanisms of 2′-FL and OPN have not been fully elucidated. To address this question, this study employed Sprague-Dawley (SD) rats to establish a lipopolysaccharide (LPS)-induced model simulating human microbiota-associated intestinal barrier damage. The findings indicate that the combined administration of 2′-FL and OPN exerts a considerable protective effect on the intestinal barrier, surpassing the individual efficacy of 2′-FL or OPN alone. The administration of 2′-FL and OPN mitigated body weight loss, attenuated disease activity index (DAI) scores, reduced serum myeloperoxidase (MPO) activity, and improved intestinal histopathology. In addition, 2′-FL and OPN significantly increased the mRNA expression of MUC2, ZO-1, and claudin-2, and reduced serum diamine oxidase (DAO) and D-lactate levels. 2′-FL and OPN reduced the levels of pro-inflammatory cytokines IL-6, and IL-1β, and elevated the levels of anti-inflammatory cytokines IL-10, IL-4, and secretory immunoglobulin A (sIgA) in the intestine. 2′-FL and OPN significantly improved the balance in CD4⁺/CD8⁺, Th1/Th2, and Th17/Treg cells. Moreover, 2′-FL and OPN regulated LPS-induced dysbiosis of the intestinal microbiota, increased the abundance of Lactobacillus and Romboutsia, and reduced the abundance of Escherichia-Shigella and Alloprevotella. Overall, 2′-FL and OPN synergistically protected against LPS-induced intestinal mucosal barrier damage in rats by regulating intestinal permeability, attenuating the inflammatory response, balancing intestinal immune cells, and modulating intestinal microbiota composition.