Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22
Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22
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乳酸菌通过 LPL 分泌 IL-22 诱导 STAT3 信号通路激活，加速 ISC 再生，保护肠粘膜完整性
DOI：
10.1038/s41418-018-0070-2
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发表时间：
2018-09-01
影响因子：
12.4
通讯作者：
Yu, Qinghua
中科院分区：
文献类型：
--
作者：
Hou, Qihang;Ye, Lulu;Yu, Qinghua
肠上皮细胞的再生是通过肠干细胞在生理和病理条件下的持续分化和增殖来维持的。然而，关于肠道菌群对其修复受损粘膜屏障恢复能力的调节作用知之甚少。本研究通过建立肠道类器官与固有层淋巴细胞（LPLs）共培养体系，并结合小鼠实验，探讨路氏乳杆菌D8对肠道黏膜完整性的保护作用。我们发现了唯一活L.在TNF-α作用下，reuteri D8可有效地保护肠类器官的形态学和EdU染色的上皮细胞的正常增殖，这一点在小鼠实验中也得到了进一步的证实。L.罗伊菌D8在肠粘膜定植，改善DSS对肠粘膜的损伤，包括体重、结肠长度、病理改变和增殖水平的改善。结果表明，L.同时，在小鼠小肠和小肠组织中Lgr 5+细胞和溶菌酶+细胞的数量也明显增加。此外，我们证明D8代谢产物吲哚-3-醛通过芳香烃受体（AhR）刺激LPL分泌IL-22，然后诱导STAT 3磷酸化，加速肠上皮细胞增殖，从而恢复受损的肠粘膜。结果表明L. reuteri保护肠道屏障并激活肠上皮细胞增殖，这为基于益生菌乳酸菌和健康食品中每日益生菌消耗的ISCs的肠道炎症治疗方法提供了启示。
The regeneration of intestinal epithelial are maintained by continuous differentiation and proliferation of intestinal stem cells (ISCs) under physiological and pathological conditions. However, little is known about the regulatory effect of intestinal microbiota on its recovery ability to repair damaged mucosal barrier. In this study, we established intestinal organoids and lamina propria lymphocytes (LPLs) co-cultured system, plus mice experiments, to explore the protective effect of Lactobacillus reuteri D8 on integrity of intestinal mucosa. We found that only live L. reuteri D8 was effective in protecting the morphology of intestinal organoids and normal proliferation of epithelial stained with EdU under TNF-α treatment, which was also further verified in mice experiments. L. reuteri D8 colonized in the intestinal mucosa and ameliorated intestinal mucosa damage caused by DSS treatment, including improvement of body weight, colon length, pathological change, and proliferation level. The repair process stimulated by L. reuteri D8 was also accompanied with increased numbers of Lgr5+and lysozyme+cells both in intestinal organoids and mice intestine. Furthermore, we demonstrated that D8 metabolite indole-3-aldehyde stimulated LPLs to secret IL-22 through aryl hydrocarbon receptor (AhR) and then induced phosphorylation of STAT3 to accelerate proliferation of intestinal epithelial, thus recovering damaged intestinal mucosa. Our findings indicate L. reuteri protects intestinal barrier and activates intestinal epithelial proliferation, which sheds light on treatment approaches for intestinal inflammation based on ISCs with probiotics Lactobacillus and daily probiotic consumption in heath foods.