Jiangxi Province Key Laboratory of Animal Nutrition and Feed, 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.
Int J Mol Sci. 2024 Oct 5;25(19):10736. doi: 10.3390/ijms251910736.
This study aimed to investigate the effects of dietary bacteriophage administration on diarrhea and intestinal impairment induced by enterotoxigenic (ETEC) in a newly weaned mouse model. Forty-four newly weaned C57BL/6 mice were divided into four treatment groups, where they were provided either the control diet or the bacteriophage-supplemented diet, with or without ETEC infection. The results show that the bacteriophage administration resulted in increased body weight, decreased diarrhea score, and improved jejunal histopathology in ETEC-infected mice. The bacteriophage administration enhanced the intestinal barrier function of the ETEC-infected mice, as indicated by the reduced serum DAO level and the increased expression of Claudin-1, Occludin, and ZO-1 at both the mRNA and protein levels in the jejunum. Also, the bacteriophage administration resulted in a decrease in serum TNF-α and IL-1β levels, a down-regulation of and mRNA levels in the jejunum, and the inhibition of jejunal TLR-4/NF-κB pathway activation induced by ETEC infection. Moreover, the bacteriophage administration increased the levels of acetic acid, propionic acid, butyric acid, and total short-chain fatty acids in the caecum content. The bacteriophage administration increased the Shannon index, increased the abundance of and , and decreased the abundance of and in the colon contents of the ETEC-infected mice. Spearman's correlation analysis indicates that the protective effects of bacteriophage on ETEC-induced intestinal impairment, inflammation, and intestinal barrier function are associated with regulating the abundance of and in the colon contents of mice. Collectively, bacteriophage administration alleviates ETEC-induced diarrhea and intestinal impairment through regulating intestinal inflammation and gut microbiota in newly weaned mice.
本研究旨在探讨饮食噬菌体给药对新生断奶小鼠肠毒素性大肠杆菌（ETEC）诱导的腹泻和肠道损伤的影响。将 44 只新生断奶 C57BL/6 小鼠分为四组治疗组，分别给予对照饮食或噬菌体补充饮食，同时或不给予 ETEC 感染。结果表明，噬菌体给药导致 ETEC 感染小鼠体重增加，腹泻评分降低，空肠组织病理学改善。噬菌体给药增强了 ETEC 感染小鼠的肠道屏障功能，表现为血清 DAO 水平降低，Claudin-1、Occludin 和 ZO-1 的 mRNA 和蛋白水平在空肠中均增加。此外，噬菌体给药还导致血清 TNF-α和 IL-1β水平降低，空肠中 和 mRNA 水平下调，以及 ETEC 感染诱导的 TLR-4/NF-κB 通路激活受到抑制。此外，噬菌体给药增加了盲肠内容物中乙酸、丙酸、丁酸和总短链脂肪酸的水平。噬菌体给药增加了 ETEC 感染小鼠结肠内容物的 Shannon 指数，增加了 和 的丰度，降低了 和 的丰度。Spearman 相关分析表明，噬菌体对 ETEC 诱导的肠道损伤、炎症和肠道屏障功能的保护作用与调节小鼠结肠内容物中 和 的丰度有关。总之，噬菌体给药通过调节新生断奶小鼠的肠道炎症和肠道微生物群缓解 ETEC 诱导的腹泻和肠道损伤。
