Study on the Synergistic Effects of Osteopontin and 2’-Fucosyllactose Combination on Intestinal Barrier Function in a Zebrafish Larval Enteritis Model
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Abstract:
Osteopontin (OPN) and 2’-fucosyllactose (2’-FL) in human milk are critical bioactive components that regulate intestinal immunity and barrier function in infants. To investigate the synergistic effects and mechanisms of OPN and 2’-FL combinations on intestinal barrier function, a zebrafish larval enteritis model induced by soybean meal was established. The study intervened with OPN and 2’-FL monomers and combinations at different ratios (1:18~1:1, m/m), and measured the number of intestinal neutrophils and goblet cells, the expression levels of inflammation- and barrier-related genes, and the protein expression levels of key cytokines. The results demonstrated that when the OPN:2’-FL ratio was 1:9~1:3 (m/m), the number of neutrophils was significantly reduced to 13.4 and 13.2 per larva, and the number of goblet cells increased to a level close to that of the normal group (95.5 per larva). Meanwhile, the gene expression levels of claudin-1/3 (CLDN1/3), zonula occludens-1 (ZO-1) and mucin 5.1 (MUC5.1) were upregulated by 3~4 fold. Additionally, the gene expression levels of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) were reduced by 47.3% and 57.1%, respectively. The immune homeostasis of the organism was improved by regulating the protein expression levels of inflammatory cytokines. In summary, the combination of OPN and 2’-FL has a significant synergistic effect on improving intestinal barrier function in zebrafish larvae with enteritis, providing a theoretical basis for the optimization of infant formula design.
