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肠道免疫和微生物群落失调与 LPS 应激仔猪胆汁酸代谢改变有关。

Gut Immunity and Microbiota Dysbiosis Are Associated with Altered Bile Acid Metabolism in LPS-Challenged Piglets.

机构信息

National Engineering Laboratory of Biological Feed Safety and Pollution Prevention and Control, Zhejiang University, Hangzhou 310058, China.

Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, Zhejiang University, Hangzhou 310058, China.

出版信息

Oxid Med Cell Longev. 2021 Mar 25;2021:6634821. doi: 10.1155/2021/6634821. eCollection 2021.

Abstract

Bacterial infections are among the major factors that cause stress and intestinal diseases in piglets. Lipopolysaccharide (LPS), a major component of the Gram-negative bacteria outer membrane, is commonly employed for inducing an immune response in normal organisms for convenience. The association between LPS stimulation and gut immunity has been reported. However, the effects of gut immunity on microbial homeostasis and metabolism of host, especially bile acid and lipid metabolism in piglets, remain unclear. Hence, in the current study, we elucidated the effect of gut immunity on microbial balance and host metabolism. Twenty-one-day-old healthy piglets (male) were randomly assigned into the CON and LPS groups. After 4 hours of treatment, related tissues and cecal contents were obtained for further analysis. The obtained results showed that stimulated LPS considerably damaged the morphology of intestinal villi and enhanced the relative expression of proinflammatory cytokines. Besides, LPS partially changed the microbial structure as indicated by -diversity and increased operational taxonomic units (OTUs) related to and . Furthermore, bile acid, a large class of gut microbiota metabolites, was also assessed by many proteins related to the enterohepatic circulation of bile acids. It was also revealed that LPS markedly inhibited the mRNA and protein expression of TGR5 and FXR (bile acid receptors) in the ileum, which expressed negative feedback on bile acid de novo synthesis. Additionally, results indicated upregulated mRNA of genes associated with the production of bile acid in the liver tissues. Moreover, LPS reduced the expression of bile acid transporters in the ileum and liver tissues and further disturbed the normal enterohepatic circulation. Taken together, gut immunity and microbial dysbiosis are associated with altered bile acid metabolism in LPS-challenged piglets, which provided theoretical basis for revealing the potential mechanism of intestinal inflammation in swine and seeking nutrients to resist intestinal damage.

摘要

细菌感染是导致仔猪应激和肠道疾病的主要因素之一。脂多糖(LPS)是革兰氏阴性细菌外膜的主要成分,通常用于在正常生物体中诱导免疫反应,以便于研究。已经报道了 LPS 刺激与肠道免疫之间的关联。然而,肠道免疫对微生物平衡和宿主代谢的影响,特别是仔猪胆汁酸和脂质代谢,尚不清楚。因此,在本研究中,我们阐明了肠道免疫对微生物平衡和宿主代谢的影响。将 21 日龄健康仔猪(雄性)随机分配到 CON 和 LPS 组。处理 4 小时后,获取相关组织和盲肠内容物进行进一步分析。结果表明,刺激 LPS 可显著破坏肠绒毛形态,并增强促炎细胞因子的相对表达。此外,LPS 部分改变了微生物结构,表现为多样性降低和与 和 相关的操作分类单元(OTUs)增加。此外,通过与胆汁酸肠肝循环相关的许多蛋白质,还评估了肠道微生物代谢产物的一大类——胆汁酸。结果还表明,LPS 显著抑制了回肠中 TGR5 和 FXR(胆汁酸受体)的 mRNA 和蛋白表达,这对胆汁酸从头合成产生了负反馈。此外,结果表明肝脏组织中与胆汁酸生成相关的基因的 mRNA 表达上调。此外,LPS 降低了回肠和肝脏组织中胆汁酸转运蛋白的表达,进一步扰乱了正常的肠肝循环。综上所述,肠道免疫和微生物失调与 LPS challenged 仔猪胆汁酸代谢改变有关,为揭示猪肠道炎症的潜在机制和寻找抵抗肠道损伤的营养物质提供了理论依据。

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