溃疡性结肠炎小鼠肠道黏膜和盲肠内容物菌群差异比较

Comparison of microflora from intestinal mucosa vs cecal contents in mice with ulcerative colitis

目的了解溃疡性结肠炎(UC)小鼠肠道黏膜菌群的构成及其与盲肠内容物菌群的差异,探讨肠道菌群在UC小鼠发病中的作用。方法12只C57BL/6N雄性小鼠随机分为正常组、治疗组和模型组,每组4只。采用葡聚糖硫酸钠盐(DSS)进行造模,采用柳氮磺胺吡啶灌胃进行治疗,造模第8天处死全部小鼠。采用16S rRNA基因高通量测序法对肠道黏膜和盲肠内容物菌群进行测序分析。结果UC小鼠肠道黏膜菌群与盲肠内容物菌群相比,OTU数量和多样性均降低;Beta多样性分析显示其黏膜和盲肠内容物菌群差异较正常小鼠更大。在门和属的分类水平上,UC小鼠黏膜菌群中变形菌门、疣微菌门、魏斯菌属和肠球菌属丰度较正常小鼠升高,厚壁菌门和拟杆菌门丰度降低;阿克曼菌属在UC小鼠黏膜和盲肠内容物菌群中增多,颤螺菌属在治疗组小鼠黏膜和盲肠内容物菌群中均减少。此外,黏膜菌群中脱铁杆菌门Mucispirillum菌属丰度较高;盲肠内容物中拟杆菌属丰度较高。物种组成分析中,颤螺菌属、Mucispirillum、志贺菌属、魏斯菌属和肠球菌属聚类在一起。结论UC小鼠黏膜菌群与盲肠内容物菌群在群落组成、多样性、优势菌群等方面存在明显差异,黏膜菌群在UC发病机制中可能发挥着主要的作用。

Objective To learn the composition of intestinal mucosal flora in mice with ulcerative colitis(UC)and the difference between intestinal mucosal flora and cecal content flora,and explore the role of intestinal mucosal flora in the pathogenesis of UC in mice.Methods Twelve male C57 BL/6 N mice were randomly divided into normal control group,treatment group or model group,with 4 mice in each group.Dextran sodium sulfate(DSS)was used for modeling and gavage with sulfasalazine for treatment.All the mice were killed on the 8 th day after modeling.The microflora in intestinal mucosa and cecum contents were sequenced using 16 S rRNA gene high-throughput sequencing method.Results The number and diversity of OTUs in intestinal mucosal flora of UC mice were lower than those in cecal contents flora.β-diversity analysis showed that the difference in the bacterial flora between mucosa and cecum contents was greater than that of normal mice.At the levels of phylum and genus,the abundances of Proteobacteria,Verrucomicrobia,Weissella and Enterococcus in UC mice were higher than those in normal mice,while those of Firmicutes and Bacteroidetes were lower.Akkermansia increased,while Oscillospira decreased in the mucosa and cecal contents of UC mice in the treatment group.In addition,the content of Mucispirillum was higher in the mucosal flora.The abundance of Bacteroidetes in cecum contents was higher.In the species composition analysis,Oscillospira,Mucispirillum,Shigella,Weissella and Enterococcus clustered together.Conclusion There are significant differences in community composition,diversity and dominant flora between the mucosal flora and cecal content flora in UC mice,and the mucosal flora may play an important role in the pathogenesis of UC.