Yan T, Zhang F, He Y, Wang X, Jin X, Zhang P, Bi D
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Lett Appl Microbiol. 2018 Nov;67(5):520-527. doi: 10.1111/lam.13067. Epub 2018 Sep 24.
Previously, we isolated a novel probiotic strain, designated HDRsEf1. In this study, we investigated the effects of this probiotic strain on intestinal barrier function and how it regulates the tight junction protein occludin in vitro. We used an ETEC-infected mouse model for the in vivo experiment. Briefly, 40 ICR mice were randomly divided into four groups: control group, assigned to saline gavage; prevention group, given HDRsEf1 before and saline after infection with ETEC; infection group, given saline both before and after infection with ETEC; treatment group, given saline before and HDRsEf1 after infection with ETEC. The weight loss was alleviated both in the prevention and treatment groups. The ETEC-induced intestinal inflammation was alleviated and the occludin mRNA expression levels in the jejuna of infected mice were increased in the prevention group. We explored the mechanism by which HDRsEf1 regulates occludin expression in vitro and found that HDRsEf1 prevented the downregulation of occludin expression in the prevention group. Simultaneously, we found that toll-like receptor-2 (TLR-2) and phosphoinositide 3-kinase (PI3K) play an important role in maintaining occludin expression. Therefore, we concluded that HDRsEf1 can prevent ETEC-induced infection by enhancing the intestinal barrier function and increasing the expression levels of occludin.
Enterotoxigenic Escherichia coli (ETEC) is a major cause of infectious diarrhoea in children, and porcine ETEC has been the leading cause of post-weaning diarrhoea (PWD) in pigs. In our present study, we demonstrated for the first time that HDRsEf1 protects occludin from ETEC-induced suppression. Moreover, HDRsEf1 was found to regulate occludin expression via TLR-2 activation and the PI3K pathway. The results provide insights into the mechanism by which HDRsEf1 protects cells against ETEC infection and a rationale for the use of HDRsEf1 as a therapeutic and preventative agent.
此前，我们分离出一种新型益生菌菌株，命名为HDRsEf1。在本研究中，我们调查了这种益生菌菌株对肠道屏障功能的影响以及它在体外如何调节紧密连接蛋白闭合蛋白。我们使用受肠毒素大肠杆菌（ETEC）感染的小鼠模型进行体内实验。简要地说，40只ICR小鼠被随机分为四组：对照组，给予生理盐水灌胃；预防组，在感染ETEC前给予HDRsEf1，感染后给予生理盐水；感染组，在感染ETEC前后均给予生理盐水；治疗组，在感染ETEC前给予生理盐水，感染后给予HDRsEf1。预防组和治疗组的体重减轻均得到缓解。预防组减轻了ETEC诱导的肠道炎症，并且感染小鼠空肠中闭合蛋白的mRNA表达水平增加。我们探究了HDRsEf1在体外调节闭合蛋白表达的机制，发现HDRsEf1可防止预防组中闭合蛋白表达的下调。同时，我们发现Toll样受体2（TLR - 2）和磷酸肌醇3激酶（PI3K）在维持闭合蛋白表达中起重要作用。因此，我们得出结论，HDRsEf1可通过增强肠道屏障功能和增加闭合蛋白表达水平来预防ETEC诱导的感染。
产肠毒素大肠杆菌（ETEC）是儿童感染性腹泻的主要原因，而猪ETEC一直是仔猪断奶后腹泻（PWD）的主要原因。在我们目前的研究中，我们首次证明HDRsEf1可保护闭合蛋白免受ETEC诱导的抑制。此外，发现HDRsEf1通过激活TLR - 2和PI3K途径调节闭合蛋白表达。这些结果为HDRsEf1保护细胞免受ETEC感染的机制提供了见解，并为将HDRsEf1用作治疗和预防剂提供了理论依据。
