甲酸、苯甲酸和三丁酸甘油酯的混合物通过调节小鼠模型中的肠道炎症和肠道微生物群来减轻ETEC K88诱导的肠道屏障功能障碍。

A blend of formic acid, benzoic acid, and tributyrin alleviates ETEC K88-induced intestinal barrier dysfunction by regulating intestinal inflammation and gut microbiota in a murine model.

作者信息

Chen Jun, Xia Yingying, Hu Youjun, Zhao Xiaolan, You Jinming, Zou Tiande

机构信息

Jiangxi Province Key Laboratory of Animal Nutrition, Jiangxi Agricultural University, Nanchang 330045, China; Jiangxi Province Key Innovation Center of Integration in Production and Education for High-quality and Safe Livestock and Poultry, Jiangxi Agricultural University, Nanchang 330045, China.

Guangdong Nuacid Biotech Co., Ltd, Qingyuan 511500, China.

出版信息

Int Immunopharmacol. 2023 Jan;114:109538. doi: 10.1016/j.intimp.2022.109538. Epub 2022 Dec 8.

DOI:10.1016/j.intimp.2022.109538

PMID:36502593

Abstract

This study aimed to investigate the effects of an organic acid (OA) blend on intestinal barrier function, intestinal inflammation, and gut microbiota in mice challenged with enterotoxigenic Escherichia coli K88 (ETEC K88). Ninety female Kunming mice (7 weeks old) were randomly allotted to five treatments with six replicates per treatment and three mice per replicate. The five treatments were composed of the non-ETEC K88 challenge group and ETEC K88 challenge + OA blend groups (0, 0.6 %, 1.2 %, and 2.4 % OA blend). The OA blend consisted of 47.5 % formic acid, 47.5 % benzoic acid, and 5 % tributyrin. The feeding trial lasted for 15 days, and mice were intraperitoneally injected with PBS or ETEC K88 solution on day 15. At 24 h post-challenge, one mouse per replicate was selected for sample collection. The results showed that a dosage of 0.6 % OA blend alleviated the ETEC K88-induced intestinal barrier dysfunction, as indicated by the elevated villus height and the ratio of villus height to crypt depth of jejunum, and the reduced serum diamine oxidase (DAO) and D-lactate levels, as well as the up-regulated mRNA levels of ZO-1, Claudin-1, and Occludin in jejunum mucosa of mice. Furthermore, dietary addition with 0.6 % OA blend decreased ETEC K88-induced inflammation response, as suggested by the decreased TNF-α and IL-6 levels, and the increased IgA level in the serum, as well as the down-regulated mRNA level of TNF-α, IL-6, IL-1β, TLR-4, MyD88, and MCP-1 in jejunum mucosa of mice. Regarding gut microbiota, the beta-diversity analysis revealed a remarkable clustering between the 0.6 % OA blend group and the ETEC K88 challenge group. Supplementation of 0.6 % OA blend decreased the relative abundance of Firmicutes, and increased the relative abundance of Bacteroidota, Desulfobacterota, and Verrucomicrobiota of colonic digesta in mice. Also, the butyric acid content in the colonic digesta of mice was increased by dietary 0.6 % OA blend supplementation. Collectively, a dosage of 0.6 % OA blend could alleviate the ETEC K88-induced intestinal barrier dysfunction by regulating intestinal inflammation and gut microbiota of mice.

摘要

本研究旨在探讨有机酸（OA）混合物对感染产肠毒素大肠杆菌K88（ETEC K88）的小鼠肠道屏障功能、肠道炎症和肠道微生物群的影响。将90只7周龄雌性昆明小鼠随机分为5组，每组6个重复，每个重复3只小鼠。5组分别为未感染ETEC K88的对照组和感染ETEC K88并添加不同剂量OA混合物的组（0、0.6%、1.2%和2.4% OA混合物）。OA混合物由47.5%的甲酸、47.5%的苯甲酸和5%的甘油三丁酸酯组成。饲养试验持续15天，在第15天给小鼠腹腔注射磷酸盐缓冲液（PBS）或ETEC K88溶液。攻毒后24小时，每组每个重复选取1只小鼠进行样本采集。结果表明，0.6%的OA混合物剂量可缓解ETEC K88诱导的肠道屏障功能障碍，表现为空肠绒毛高度增加、绒毛高度与隐窝深度比值升高，血清二胺氧化酶（DAO）和D-乳酸水平降低，以及小鼠空肠黏膜中紧密连接蛋白1（ZO-1）、闭合蛋白1（Claudin-1）和封闭蛋白（Occludin）的mRNA水平上调。此外，添加0.6%的OA混合物可降低ETEC K88诱导的炎症反应，表现为血清中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平降低、免疫球蛋白A（IgA）水平升高，以及小鼠空肠黏膜中TNF-α、IL-6、白细胞介素-1β（IL-1β）、Toll样受体4（TLR-4）、髓样分化因子88（MyD88）和单核细胞趋化蛋白-1（MCP-1）的mRNA水平下调。关于肠道微生物群，β-多样性分析显示0.6% OA混合物组和ETEC K88感染组之间有明显的聚类。添加0.6%的OA混合物可降低小鼠结肠内容物中厚壁菌门的相对丰度，并增加拟杆菌门、脱硫杆菌门和疣微菌门的相对丰度。此外，添加0.6%的OA混合物可增加小鼠结肠内容物中的丁酸含量。综上所述，0.6%的OA混合物剂量可通过调节小鼠肠道炎症和肠道微生物群来缓解ETEC K88诱导的肠道屏障功能障碍。