关键词: 氧化锌；断奶仔猪；肠道屏障；细胞外基质；门静脉；代谢组学

Abstract: This study aimed to investigate the effects of dietary supplementation with 1 500 mg/kg zinc oxide （ZnO）on the small intestinal mucosal barrier，extracellular matrix（ECM）remodeling，and serum metabolic profiles in the portal vein and anterior vena cava in weaned piglets. A total of 72 28?day?old weaned piglets were randomly assigned to a control group（CON）and ZnO group，with six replicates per group and six piglets per replicate. Piglets in the CON group were fed a basal diet，while the ZnO group received the basal diet supplemented with 1 500 mg/kg ZnO for a feeding trial lasting 28 days. The mRNA expression levels of genes related to intestinal barrier，inflammation and ECM in the jejunal and ileal mucosa were determined by qPCR. Non ? targeted metabolomics and pathway enrichment analysis were performed on serum samples from the portal vein and anterior vena cava. The results showed that，compared with the CON group，the ZnO group exhibited upregulated expression of the intestinal barrier genes ZO?1 and Occludin，increased expression of the anti?inflammatory gene IL?4，downregulated COL4 and upregulated COL5 in the jejunum. In the ileum，COL4 and COL6 were downregulated，whereas COL5 was upregulated； meanwhile，the expression of inflammatory genes IL ? 6 and IL ? 10 was decreased，and MMP9 expression was increased. Metabolomic analysis indicated that arginine biosynthesis and pantothenate/CoA biosynthesis were the two most significantly altered pathways in the portal vein. In the anterior vena cava，the differentially enriched pathways mainly included nitrogen metabolism and arginine biosynthesis. Moreover，the arginine biosynthesis pathway was closely associated with ECM and participated in ECM remodeling. Correlation analysis between metabolites and target genes further verified that ZnO could regulate extracellular matrix by modulating the dynamic expression of key metabolites，thereby affecting the occurrence of diarrhea in weaned piglets. In conclusion，dietary supplementation with 1500 mg/kg ZnO improved the expression of tight junction proteins，regulated inflammatory responses，induced ECM remodeling in the small intestine，and reshaped metabolic characteristics of portal vein and systemic circulation. ZnO?mediated ECM regulation depended on the dynamic changes of metabolites，which may be related to metabolic regulation via the gut-liver axis.

Key words: Zinc oxide；Weaned piglets；Intestinal barrier；Extracellular matrix；Portal vein；Metabolomics