Gut microbiota imbalance mediates intestinal barrier damage in high‐altitude exposed mice
Gut microbiota imbalance mediates intestinal barrier damage in high‐altitude exposed mice
复制标题
DOI：
10.1111/febs.16409
复制
发表时间：
2022-02
期刊：
影响因子：
--
通讯作者：
Yuhao Wang;Yi Shi;Wenhao Li;Shu Wang;Ji-yang Zheng;Guanghui Xu;Guixiang Li;Xuefeng Shen;Jianjun Yang
中科院分区：
文献类型：
--
作者：
Yuhao Wang;Yi Shi;Wenhao Li;Shu Wang;Ji-yang Zheng;Guanghui Xu;Guixiang Li;Xuefeng Shen;Jianjun Yang
高海拔地区的环境条件会诱发胃肠道疾病和肠道微生物群的变化。肠道微生物群与各种胃肠道疾病密切相关，尽管潜在的致病机制尚未得到很好的鉴定。本研究旨在通过肠道菌群失调来探讨高原对肠道功能障碍的调节作用。将40只C57 BL/6 J小鼠分为4组：1个平原对照组（CON）和3个高海拔暴露组（HAE）（海拔：4000 m a.s.l.;氧含量：12.7%; 1、2和4周暴露）。将另一组40只小鼠分成两个CON和两个HAE亚组。将抗生素混合物分别给予一个CON和HAE组，并将高压灭菌水分别给予第二个CON和HAE组4周。在粪便微生物群移植实验中，有四个移植组，分别接受：磷酸盐缓冲盐水2周、CON粪便2周、HAE-4 W粪便2周和HAE-4 W粪便4周。应用苏木精和伊红染色、过碘酸-希夫染色、末端脱氧核苷酸转移酶dUTP缺口末端标记法和定量逆转录酶-聚合酶链反应检测肠细胞结构、形态、细胞凋亡和肠道炎症反应的变化。使用16 S rDNA扩增子测序分析粪便微生物群。高海拔环境改变了小鼠肠道微生物群的生态平衡，并对肠道结构和粘膜屏障造成损害。有趣的是，在移植了来自HAE的粪便微生物群的小鼠中观察到了类似的损伤，这种损伤在高海拔地区被抗生素鸡尾酒抑制。高海拔环境导致肠道微生物群平衡失调，从而损害肠粘膜屏障，最终诱导和加剧肠道损伤。
The environmental conditions in high‐altitude areas can induce gastrointestinal disorders and changes in gut microbiota. The gut microbiota is closely related to a variety of gastrointestinal diseases, although the underlying pathogenic mechanisms are not well‐identified. The present study aimed to investigate the regulatory effect of high altitude on intestinal dysfunction via gut microbiota disturbance. Forty C57BL/6J mice were divided into four groups: one plain control group (CON) and three high‐altitude exposure groups (HAE) (altitude: 4000 m a.s.l.; oxygen content: 12.7%; 1‐, 2‐ and 4‐week exposure). Another set of 40 mice was divided into two CON and two HAE subgroups. Antibiotic cocktails were administered to one CON and HAE groups and autoclaved water was administered to the second CON and HAE groups for 4 weeks, respectively. In the fecal microbiota transplantation experiment, there were four transplantation groups, which received, respectively: phosphate‐buffered saline for 2 weeks, feces from CON for 2 weeks, feces from HAE‐4W for 2 weeks, and HAE‐4W for 4 weeks. Hematoxylin and eosin staining, periodic acid–Schiff staining, a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and a quantitative reverse transcriptase‐polymerase chain reaction were applied to detect changes in intestinal cellular structure, morphology, apoptosis and intestinal inflammatory response. Fecal microbiota was analyzed using 16S rDNA amplicon sequencing. A high‐altitude environment changed the ecological balance of gut microbiota in mice and caused damage to the intestinal structure and mucosal barrier. Interestingly, similar damage, which was inhibited by antibiotic cocktails at high altitude, was observed in mice transplanted with fecal microbiota from HAE. A high‐altitude environment contributes to dyshomeostasis of gut microbiota, thereby impairing the intestinal mucosal barrier, eventually inducing and exacerbating intestinal damage.