Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, is the main medicinal component of bear bile and is commonly used to treat a variety of hepatobiliary diseases. Meanwhile, TUDCA has been shown to modulate the intestinal barrier function and alleviate DSS-induced colitis in mice. However, the effect of TUDCA on the intestinal barrier of weaned piglets remains largely unclear. The weaned piglets and porcine IPEC-J2 intestinal epithelial cells were used to investigate the effects of TUDCA on intestinal barrier function in weaned piglets and explore the possible underlying mechanisms. In vivo, 72 healthy weaned piglets were randomly allocated into 2 groups according to their gender and body weight, and piglets were fed the basal diet with 0 (control, CON) and 200 mg/kg TUDCA for 30 d, respectively. Three female and three male piglets reflecting the average bodyweight were slaughtered in each group and samples were collected. In vitro, IPEC-J2 cells were subjected to 100 μmol/L TUDCA to explore the possible underlying mechanisms. Our results demonstrated that dietary TUDCA supplementation significantly reduced the diarrhea incidence of weaned piglets, possibly attributing to the TUDCA-enhanced intestinal barrier function and immunity. In addition, TUDCA supplementation altered serum metabolites and the relative abundance of certain gut bacteria, which might contribute to the improved intestinal barrier function. Furthermore, the in-vitro results showed that TUDCA improved the E. coli-induced epithelial barrier impairment of IPEC-J2 cells and increased Takeda G-coupled protein receptor 5 (TGR5) protein expression. However, knockdown of TGR5 and inhibition of myosin light chain kinase (MLCK) pathway abolished the TUDCA-improved epithelial barrier impairment in E. coli-treated IPEC-J2 cells, indicating the involvement of TGR5-MLCK in this process. These findings showed that TUDCA improved intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets, suggesting the potential application of TUDCA in improving gut health in piglet production.

中文翻译：

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牛磺熊去氧胆酸 (TUDCA) 改善与 TGR5-MLCK 通路相关的肠道屏障功能以及断奶仔猪血清代谢物和肠道细菌的改变

牛磺熊去氧胆酸（TUDCA）是一种亲水性胆汁酸，是熊胆汁的主要药用成分，常用于治疗多种肝胆疾病。同时，TUDCA 已被证明可调节肠道屏障功能并减轻 DSS 诱导的小鼠结肠炎。然而，TUDCA 对断奶仔猪肠道屏障的影响仍不清楚。使用断奶仔猪和猪IPEC-J2肠上皮细胞研究TUDCA对断奶仔猪肠道屏障功能的影响，并探讨可能的潜在机制。在体内，将72头健康断奶仔猪根据性别和体重随机分为2组，分别饲喂0（对照，CON）和200 mg/kg TUDCA基础日粮30 d。每组屠宰反映平均体重的3头母猪和3头公猪并采集样本。在体外，IPEC-J2 细胞经受 100 μmol/L TUDCA 以探索可能的潜在机制。我们的研究结果表明，日粮补充 TUDCA 显着降低了断奶仔猪的腹泻发生率，这可能归因于 TUDCA 增强的肠道屏障功能和免疫力。此外，TUDCA 补充剂改变了血清代谢物和某些肠道细菌的相对丰度，这可能有助于改善肠道屏障功能。此外，体外结果表明，TUDCA 改善了大肠杆菌诱导的 IPEC-J2 细胞上皮屏障损伤，并增加了武田 G 偶联蛋白受体 5 (TGR5) 蛋白的表达。然而，TGR5 的敲低和肌球蛋白轻链激酶 (MLCK) 通路的抑制消除了大肠杆菌处理的 IPEC-J2 细胞中 TUDCA 改善的上皮屏障损伤，表明 TGR5-MLCK 参与了该过程。这些发现表明，TUDCA 改善了与 TGR5-MLCK 通路相关的肠道屏障功能以及断奶仔猪血清代谢物和肠道细菌的改变，表明 TUDCA 在改善仔猪生产中肠道健康方面的潜在应用。