应用16S rRNA基因测序比较分析不同品系1型糖尿病小鼠肠道菌群的异同  

Use of 16S rRNA Sequencing for Comparative Analysis of Gut Microbiome in Different Strains of Type 1 Diabetic Mice

作　　者：刘军[1] 丁登峰 高伟[1] 陈华[1] 牛苗苗 LIU Jun;DING Dengfeng;GAO Wei;CHEN Hua;NIU Miaomiao(the PLA General Hospital,Beijing 100853,China)

机构地区：[1]中国人民解放军总医院,北京100853

出　　处：《实验动物科学》2023年第5期24-32,共9页Laboratory Animal Science

基　　金：军队实验动物专项科研课题(SYDW[2020]01,SYDW[2020]02)。

摘　　要：目的比较C57BL/6(B6)和FVB两个品系小鼠建立的1型糖尿病(T1DM)模型肠道菌群组成和多样性的异同,为探索两模型在T1DM相关肠道菌群研究中的进一步应用提供背景数据。方法采用8周龄SPF级雄性B6和FVB小鼠各20只,两组小鼠每天腹腔注射40 mg/kg的链脲佐菌素(STZ)连续5 d,小鼠空腹血糖连续2周≥11.1 mmol/L为T1DM建模成功,建模6周后每组分别收集10份洁净粪便,进行16S rRNA基因V3-V4区测序,分析粪便中肠道菌群的Alpha多样性、Beta多样性、优势菌科及肠道菌群相关的功能通路。结果B6与FVB组T1DM小鼠肠道菌群的Alpha多样性和丰富度没有显著差异(P>0.05),两组小鼠的菌群Beta多样性存在统计学上的差异(P<0.05)。B6组T1DM小鼠肠道的优势菌科为Muribaculaceae、Lactobacillaceae、Lachnospiraceae、Prevotellaceae、Desulfovibrionaceae、Akkermansiaceae;FVB组T1DM小鼠肠道的优势菌科为Lactobacillaceae、Muribaculaceae、Lachnospiraceae、Prevotellaceae、Clostridiales_unclassified、Saccharimonadaceae、Marinifilaceae;两组中共有的优势菌科在比例上差异很大。B6与FVB组的厚壁菌门与拟杆菌门的比值都显著增加。两组T1DM小鼠肠道菌群的功能通路集中在以氨基酸、糖代谢及核苷酸的代谢途径中。结论两组T1DM小鼠肠道菌群Alpha多样性无差异,但肠道菌群的组成及比例差异较大,优势菌群在不同模型中的组成比例发生了改变。Objective To compare the composition and diversity of the Gut microbiota of type 1 diabetes mellitus(T1DM)established by C57BL/6(B6)and FVB mice,and to provide some basic data for further application of the two models in the study of T1DM-related Gut microbiota.Method Forty 8-week old SPF mice were divided into B6 group(n=20)and FVB group(n=20),respectively.The two groups of mice were intraperitoneally injected with streptozotocin(40 mg/kg)daily for 5 consecutive days,and fasting blood glucose≥11.1 mmol/L for 2 consecutive weeks was considered as T1DM mice.After 6 weeks of modeling,10 fecal samples were collected from each group,and 16S rRNA gene V3-V4 region was sequenced,the Alpha diversity,Beta diversity,dominant families and the functional pathways related to gut microbiota in fecal were analyzed.Result There was no difference in alpha diversity and richness between B6 and FVB T1DM mice(all P>0.05),and beta diversity was significantly different in the two groups(all P<0.05).The dominant families of T1DM mice in B6 group were Muribaculaceae,Lactobacillaceae,Lachnospiraceae,Prevotellaceae,Desulfovibrionaceae and Akkermansiaceae.And the dominant families of T1DM mice in FVB group were Lactobacillaceae、Muribaculaceae、Lachnospiraceae、Prevotellaceae、Clostridiales_unclassified、Saccharimonadaceae and Marinifilaceae.The proportion of the same dominant bacterial families was a significant difference between the two groups.The ratio of Firmicutes to Bacteroidetes were increased significantly in B6 and FVB groups.The functional pathways of the gut microbiome of T1DM mice in the two groups were concentrated in the metabolic pathways with amino acid,sugar metabolism and nucleotide metabolism.Conclusion There was no difference in alpha diversity of gut microbiome between B6 and FVB groups of T1DM mice,but the composition and proportion of gut microbiome were significantly different.The composition proportion of the dominant gut microbiome was changed in the different models.

关 键 词：C57BL/6 FVB 1型糖尿病 肠道菌群 多样性 16S rRNA基因测序 

分 类 号：Q95-3[生物学—动物学]