高原低氧小鼠肠道菌群在粪菌移植过程中的特征性变化研究

Study on characteristic changes in high-altitude hypoxic gut microbiota during fecal microbiota transplantation

目的探讨高原低氧肠道菌群在移植过程中作用持续时间和菌群的动态变化。方法①构建高原低氧模型:雄性C57BL/6J小鼠随机分为平原组(P组)和低氧组(H-4W组),每组6只。H-4W组模拟海拔4000 m暴露4周。②构建粪菌移植模型:雄性C57BL/6J小鼠随机分为对照组(Con组)、粪菌移植平原组(FMT-P组)和粪菌移植低氧组(FMT-H组),每组6只。FMT-P组和FMT-H组饮用抗生素鸡尾酒2周,粪菌移植2周,持续自由定植2周。16S rDNA检测肠道菌群变化情况。结果与P组相比,H-4W组肠道菌群Shannon指数和Simpson指数显著降低(P<0.05),alpha多样性降低;菌群组成结构改变(P<0.01)。粪菌移植后,FMT-H组相较于FMT-P组肠道菌群alpha多样性显著降低(P<0.01),致病菌拟杆菌属和Escherichia-Shigella菌属丰度增加,有益菌Lachnospiraceae_NK4A136_group菌属丰度降低;菌群定植2周后,两组间alpha多样性仍具有显著差异(P<0.01)。结论高原低氧暴露的肠道菌群在受体体内自由定植2周后仍具有效果,且肠道菌群紊乱可能与高原低氧环境中肠道炎症有关。

Objective To investigate the duration of action and microbial dynamic changes of high-altitude hypoxic gut microbiota during transplantation.Methods①Establishment of a model for high-altitude hypoxia:the male C57BL/6J mice were randomly divided into plain group(P group)and hypoxia group(H-4W group),with 6 mice in each group.The H-4W group was exposed to a simulated altitude of 4000 m for 4 weeks.②Establishment of a model for fecal microbiota transplantation:the male C57BL/6J mice were randomly divided into control group(Con group),fecal microbiota transplantation plain group(FMT-P group)and fecal microbiota transplantation hypoxia group(FMT-H group),with 6 mice in each group.FMT-P group and FMT-H group were given antibiotic cocktail for 2 weeks,fecal microbiota transplantation for 2 weeks,and continued colonization for 2 weeks.16S rDNA was used to detect the changes of gut microbiota.Results Compared with P group,the H-4W group had significant decreases in Shannon diversity index and Simpson diversity index(P<0.05)and alpha diversity.The composition and structure of gut microbiota were changed(P<0.01).After fecal microbiota transplantation,the alpha diversity of gut microbiota in FMT-H group was significantly lower than that in FMT-P group(P<0.01),the abundance of pathogenic bacteria Bacteroides and Escherichia-Shigella increased,and the abundance of beneficial bacteria Lachnospiraceae_NK4A136_group decreased.After 2 weeks of colonization,there was still a significant difference in alpha diversity between the two groups(P<0.01).Conclusion The gut microbiota exposed to high-altitude hypoxia still has an effect after 2 weeks of colonization in the recipients,and the disturbances of gut microbiota may be related to intestinal inflammation in high altitude hypoxia environment.