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牛磺熊去氧胆酸(TUDCA)可改善断奶仔猪肠道屏障功能,这与TGR5-MLCK途径以及血清代谢物和肠道细菌的变化有关。

Tauroursodeoxycholic acid (TUDCA) improves intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets.

作者信息

Song Min, Zhang Fenglin, Fu Yiming, Yi Xin, Feng Shengchun, Liu Zhichang, Deng Dun, Yang Qiang, Yu Miao, Zhu Canjun, Zhu Xiaotong, Wang Lina, Gao Ping, Shu Gang, Ma Xianyong, Jiang Qingyan, Wang Songbo

机构信息

Guangdong Provincial Key Laboratory of Animal Nutrition Control, ALLTECH-SCAU Animal Nutrition Control Research Alliance, and National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, P. R. China.

Institute of Animal Science, Guangdong Academy of Agricultural Sciences, State Key Laboratory of Livestock and Poultry Breeding, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture and Rural Affairs, Guangdong Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat Quality and Safety Control and Evaluation, Guangzhou, 510640, P. R. China.

出版信息

J Anim Sci Biotechnol. 2022 Jun 8;13(1):73. doi: 10.1186/s40104-022-00713-3.

DOI:10.1186/s40104-022-00713-3
PMID:35672805
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9175448/
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

牛磺熊去氧胆酸(TUDCA)是一种亲水性胆汁酸,是熊胆的主要药用成分,常用于治疗各种肝胆疾病。同时,TUDCA已被证明可调节肠道屏障功能并减轻小鼠DSS诱导的结肠炎。然而,TUDCA对断奶仔猪肠道屏障的影响仍不清楚。

方法

采用断奶仔猪和猪IPEC-J2肠上皮细胞,研究TUDCA对断奶仔猪肠道屏障功能的影响,并探讨其潜在机制。在体内,将72只健康断奶仔猪按性别和体重随机分为2组,分别饲喂含0(对照,CON)和200mg/kg TUDCA的基础日粮30天。每组宰杀反映平均体重的3只雌性和3只雄性仔猪并采集样本。在体外,用100μmol/L TUDCA处理IPEC-J2细胞以探讨潜在机制。

结果

我们的结果表明,日粮中添加TUDCA可显著降低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,添加TUDCA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蛋白偶联受体5(TGR5)蛋白表达。然而,敲低TGR5和抑制肌球蛋白轻链激酶(MLCK)途径消除了TUDCA改善的大肠杆菌处理的IPEC-J2细胞上皮屏障损伤,表明TGR5-MLCK参与了这一过程。

结论

这些发现表明,TUDCA改善了断奶仔猪与TGR5-MLCK途径相关的肠道屏障功能以及血清代谢物和肠道细菌的改变,提示TUDCA在改善仔猪生产中肠道健康方面的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/327401fb363c/40104_2022_713_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/265ccd3ca890/40104_2022_713_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/54b3b21916d0/40104_2022_713_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/0d58141cfe97/40104_2022_713_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/ac9801976aa9/40104_2022_713_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/525b95e9605b/40104_2022_713_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/133453bf95b0/40104_2022_713_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/c5297ca0d72f/40104_2022_713_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/39d70af48d9e/40104_2022_713_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/327401fb363c/40104_2022_713_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/265ccd3ca890/40104_2022_713_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/54b3b21916d0/40104_2022_713_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/0d58141cfe97/40104_2022_713_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/ac9801976aa9/40104_2022_713_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/525b95e9605b/40104_2022_713_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/133453bf95b0/40104_2022_713_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/c5297ca0d72f/40104_2022_713_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/39d70af48d9e/40104_2022_713_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/114b/9175448/327401fb363c/40104_2022_713_Fig9_HTML.jpg

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