Ovotransferrin ameliorated intestinal barrier dysfunction in DSS-induced ulcerative colitis mice via inhibition of PI3K-Akt/MAPK signaling pathways and modulation of tissue metabolism.

Ovotransferrin (OVT), a bioactive protein from egg white, has been demonstrated to exhibit anti-inflammatory efficacy and suppress the progression of ulcerative colitis. Nevertheless, its role in preserving intestinal barrier integrity has not been reported. This study investigated the role of OVT on intestinal barrier dysfunction in DSS-induced ulcerative colitis mice and its underlying mechanisms. OVT significantly attenuated the severity of intestinal barrier injury, reduced inflammatory infiltration, and restored goblet cell density (Model: 5.00 goblet cells/crypt, High: 12.75 goblet cells/crypt) alongside the expression of MUC2 (87.64 %), ZO-1 (83.98 %), and Occludin (74.93 %). Concurrently, OVT decreased intestinal permeability by 84.42 %. Furthermore, OVT downregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), while elevating anti-inflammatory IL-10 levels and restoring redox homeostasis. RNA-seq and Western blot analysis revealed that OVT inhibited the PI3K-Akt/MAPK pathway by decreasing the phosphorylation of p85α (31.73 %), Akt (69.59 %), p38 (25.00 %), and ERK (41.18 %). Metabolomics showed that OVT modulated key metabolites, including L-glutamate, serotonin, and d-fructose-6-phosphate, while decreasing glucose and L-asparagine. These results suggested that OVT regulated immune responses and metabolic pathways, highlighting its therapeutic potential in preserving intestinal barrier integrity.