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

摘要： 该试验旨在研究日粮添加1 500 mg/kg氧化锌（ZnO）对断奶仔猪小肠黏膜屏障、细胞 外基质（Extracellularmatrices，ECM）重塑及门静脉/前腔静脉血清代谢谱的影响。试验选择72 头28日龄断奶仔猪随机分为CON组与ZnO组（6重复×6头），CON组饲喂基础日粮，ZnO组基 础日粮中再添加1 500 mg/kg氧化锌，饲养试验期为28天。采用qPCR检测空肠、回肠黏膜屏 障/炎症与ECM基因；分析门静脉和前腔静脉血清的非靶向代谢组学与通路富集。结果显示， 与CON相比，ZnO组空肠肠道屏障基因（ZO?1）、Occludin 上调，炎症因子基因IL?4 上调，COL4 下调、COL5 上调；回肠COL4 与COL6 下调、COL5 上调，并伴炎症因子基因IL?6、IL?10 下降及 MMP9 升高。代谢组学结果分析得出门静脉通路改变以精氨酸合成与泛酸/CoA合成两条通路 最显著；前腔静脉涉及氮代谢与精氨酸生物合成两条通路，且精氨酸生物合成通路同ECM相 关，参与ECM重塑。代谢物与基因相关性分析也表明，氧化锌可通过影响部分代谢物动态表 达来调控细胞外基质，进而影响仔猪腹泻。由此可见，1 500 mg/kg ZnO处理可改善仔猪空肠紧 密连接表达并调节炎症信号，诱导小肠中ECM重排，并重塑门静脉及体循环代谢特征，进而 通过影响代谢物动态表达调控细胞外基质，提示其可能与肠—肝轴代谢调控相关。

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