植物乳杆菌通过激活肠上皮细胞中的 FXR-FGF15 信号传导来减轻辐射诱导的肠损伤,Journal of Cellular Physiology

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植物乳杆菌通过激活肠上皮细胞中的 FXR-FGF15 信号传导来减轻辐射诱导的肠损伤
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2021-12-08 , DOI: 10.1002/jcp.30651
Yong-Ping Jian ₁ , Ge Yang ₁ , Li-Hong Zhang ₁ , Ji-Yong Liang ₂ , Hong-Lan Zhou ₃ , Yi-Shu Wang ₁ , Zhi-Xiang Xu _{1,

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Affiliation

腹部照射（IR）可能会破坏肠黏膜屏障，导致严重的肠道感染和多器官功能障碍综合征。肠道微生物群在 IR 诱导的肠道损伤发展中的作用仍然很大程度上未知。在此，我们报道了腹部 IR 改变了微生物群的组成并降低了肠道微生物组的丰度和多样性。细菌的改变，特别是乳酸杆菌的减少，在 IR 诱导的肠道损伤中起关键作用。来自正常小鼠的粪便微生物群移植 (FMT) 或向肠道微生物群消除的小鼠施用植物乳杆菌可显着减少 IR 诱导的肠道损伤并防止小鼠死于 IR 诱导的死亡。我们进一步表征了植物乳杆菌激活肠上皮细胞中的法尼醇 X 受体 (FXR) – 成纤维细胞生长因子 15 (FGF15) 信号传导，从而促进 DNA 损伤修复。将 FXR 的激活剂 GW4064 应用于微生物群可消除小鼠，显着减轻 IR 诱导的肠道损伤，减少肠上皮细胞死亡并促进 IR 小鼠的存活。相比之下，用 Gly-β-MCA（一种胆汁酸和一种肠道选择性和高亲和力 FXR 抑制剂）抑制 FXR，消除了植物乳杆菌介导的对 IR 小鼠回肠的保护。总之，我们的研究结果不仅为肠道菌群在辐射引起的肠道损伤中的作用提供了新的见解，而且为益生菌在保护辐射损伤个体中的应用提供了新的思路。

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Lactobacillus plantarum alleviates irradiation-induced intestinal injury by activation of FXR-FGF15 signaling in intestinal epithelia

Abdominal irradiation (IR) may destroy the intestinal mucosal barrier, leading to severe intestinal infection and multiple organ dysfunction syndromes. The role of intestinal microbiota in the development of IR-induced intestinal injury remains largely unknown. Herein, we reported that abdominal IR altered the composition of the microbiota and reduced the abundance and diversity of the gut microbiome. Alterations of bacteria, in particular reduction of Lactobacillus, played a critical role in IR-induced intestinal injury. Fecal microbiota transplant (FMT) from normal mice or administration of Lactobacillus plantarum to intestinal microbiota-eliminated mice substantially reduced IR-induced intestinal damage and prevented mice from IR-induced death. We further characterized that L. plantarum activated the farnesoid X receptor (FXR) – fibroblast growth factor 15 (FGF15) signaling in intestinal epithelial cells and hence promoted DNA-damage repair. Application of GW4064, an activator of FXR, to microbiota eliminated mice markedly mitigated IR-induced intestinal damage, reduced intestinal epithelial cell death and promoted the survival of IR mice. In contrast, suppression of FXR with Gly-β-MCA, a bile acid and an intestine-selective and high-affinity FXR inhibitor, abrogated L. Plantarum-mediated protection on the ileum of IR mice. Taken together, our findings not only provide new insights into the role of intestinal flora in radiation-induced intestinal injury but also shed new light on the application of probiotics for the protection of radiation-damaged individuals.

更新日期：2021-12-08

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