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罗伊氏乳杆菌通过激活 Wnt/β-连环蛋白信号通路刺激肠道干细胞的扩增来减轻 LPS 诱导的肉鸡肠道黏膜损伤。

Lactobacillus reuteri alleviates LPS-induced intestinal mucosal damage by stimulating the expansion of intestinal stem cells via activation of the Wnt/β-catenin signaling pathway in broilers.

机构信息

Key Laboratory of Animal Nutrition and Feed in East China, Ministry of Agriculture and Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Feed Science Institute, College of Animal Science, Zhejiang University (Zijingang Campus), Hangzhou 310058, China.

Key Laboratory of Animal Nutrition and Feed in East China, Ministry of Agriculture and Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Feed Science Institute, College of Animal Science, Zhejiang University (Zijingang Campus), Hangzhou 310058, China.

出版信息

Poult Sci. 2024 Oct;103(10):104072. doi: 10.1016/j.psj.2024.104072. Epub 2024 Jul 8.

DOI:10.1016/j.psj.2024.104072
PMID:39068698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11332868/
Abstract

The continuous expansion of intestinal stem cells (ISCs) is crucial for maintaining the renewal of the intestinal epithelium, particularly in inflammatory conditions. It remains largely unknown how the internal microbiota repair damage to the internal mucosal barrier. Hence, investigating potential anti-inflammatory probiotics from the intestinal symbolic microbes of broilers and analyzing their mechanism of action to support the intestinal mucosal barrier function can offer novel regulatory tools to alleviate broiler enteritis. In this research, we utilized in vivo broilers plus ex vivo organoids model to thoroughly examine the effectiveness of Lactobacillus reuteri (LR) in protecting the integrity of the intestinal mucosa during lipopolysaccharide-induced (LPS-induced) enteritis in broilers. The findings indicated that LR feeding maintained intestinal morphological and structural integrity, enhanced proliferation of intestinal epithelial cells, and inhibited cell apoptosis and inflammatory response against the deleterious effects triggered by LPS. Simultaneously, LR enhanced ISCs activity and stimulated intestinal epithelial regeneration to protect the intestinal barrier during LPS-induced injury conditions. The coculture system of LR and ileum organoids revealed that LR increased the growth of organoids and attenuated LPS-stimulated damage to organoids. Furthermore, the LPS-induced decrease in ISC activity was rescued by reactivation of Wnt/β-catenin signaling by LR ex vivo and in vivo. This research revealed that LR promoted the expansion of ISCs and intestinal epithelial cell renewal by regulating the Wnt/β-catenin signaling pathway, thereby maintaining the integrity of the intestinal mucosal barrier. This finding provided theoretical support for lactobacillus as a probiotic additive in livestock feed to improve intestinal inflammation and treat intestinal diseases.

摘要

肠干细胞(ISCs)的持续扩增对于维持肠道上皮的更新至关重要,特别是在炎症情况下。内部微生物群如何修复内部黏膜屏障的损伤在很大程度上仍不清楚。因此,从肉鸡的肠道共生微生物中寻找潜在的抗炎益生菌,并分析其作用机制以支持肠道黏膜屏障功能,可以为缓解肉鸡肠炎提供新的调控工具。在这项研究中,我们利用体内肉鸡加体外类器官模型,深入研究了在 LPS 诱导的肉鸡肠炎中,鼠李糖乳杆菌(LR)保护肠道黏膜完整性的有效性。研究结果表明,LR 喂养维持了肠道的形态和结构完整性,增强了肠道上皮细胞的增殖,并抑制了细胞凋亡和炎症反应,从而减轻了 LPS 引发的损伤。同时,LR 增强了 ISC 活性,并刺激了肠道上皮细胞的再生,以保护肠道屏障免受 LPS 诱导的损伤。LR 和回肠类器官的共培养系统表明,LR 促进了类器官的生长,并减轻了 LPS 对类器官的刺激损伤。此外,LR 通过体外和体内激活 Wnt/β-catenin 信号通路,挽救了 LPS 诱导的 ISC 活性降低。这项研究揭示了 LR 通过调节 Wnt/β-catenin 信号通路促进 ISC 的扩增和肠道上皮细胞的更新,从而维持肠道黏膜屏障的完整性。这一发现为将乳酸菌作为一种益生菌添加剂添加到牲畜饲料中,以改善肠道炎症和治疗肠道疾病提供了理论支持。

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