标题：二甲双胍对糖尿病小鼠肠道菌群影响的高通量测序研究

      作者：刘慧云，谢强，涂忠亮    丰城市人民医院内分泌科，江西 宜春 331100

      卷次： 2020年31卷23期

      【摘要】 目的 研究二甲双胍对糖尿病小鼠肠道菌群的影响。方法 SPF级 ICR雄性小鼠9只，体质量22 g左右，随机选3只作为对照组(BMCK、M2WCK和M42CK)，其余6只高糖高脂饮食饲养4周后腹腔注射四氧嘧啶溶液引发胰岛损伤后完成糖尿病小鼠造模。6只糖尿病小鼠随机均分为二甲双胍治疗组(BMMet、M2WMet和M42Met)和模型组(BMMod、M2WMod和M42Mod)各 3只。二甲双胍治疗组给予每日两次二甲双胍灌胃，对照组和模型组给予生理盐水灌胃。4周后取粪便提取微生物总RNA，进行 16S高通量测序，进行菌群多样性分析。结果 肠道微生物 16S测序分类鉴定统计结果显示，各组样品测序结果已足够反映当前样本所包含的多样性；3个糖尿病模型组小鼠肠道微生物中都出现了乳酸杆菌属微生物显著减少的情况，而其中两个出现了异杆菌属(Allobaculum)微生物增多的情况；而 3个二甲双胍治疗糖尿病组小鼠肠道微生物中都出现了乳酸杆菌属微生物恢复性增多的现象；此外，二甲双胍处理还让糖尿病小鼠肠道中梭菌属和拟杆菌属微生物丰度向正常状态转变。结论 受二甲双胍影响，糖尿病小鼠肠道菌群微生物会更倾向抑制脂肪代谢减轻肥胖，这种作用可能有助于治疗糖尿病。
      【关键词】 糖尿病；肠道微生物；16s测序；二甲双胍；乳酸杆菌
      【中图分类号】 R-332 【文献标识码】 A 【文章编号】 1003—6350（2020）23—2998—06

High throughput sequencing of effect of metformin on intestinal flora in diabetic mice.
LIU Hui-yun, XIE Qiang,TU Zhong-liang. Depatment of Fengcheng People's Hospital, Yichun 331100, Jiangxi, CHINA
【Abstract】 Objective To study the effect of metformin on intestinal flora of diabetic mice. Methods A totalof 9 SPF grade ICR male mice, weighing about 22 g, were randomly selected as the control group (BMCK, M2WCKand M42CK), and the remaining 6 mice were intraperitoneally injected with alloxan solution for 4 weeks after feedingon a high-sugar and high-fat diet to induce islet injury and complete the modeling of diabetic mice. Diabetic mice wererandomly divided into the metformin treatment group (BMMet, M2WMet, and M42Met) and the model group (BMMod,M2WMod, and M42Mod). Metformin was given twice daily to the metformin treatment group, and normal saline wasgiven to the control group and the model group. After 4 weeks, total RNA of microorganisms was extracted from feces,and 16S high-throughput sequencing was carried out to analyze the diversity of bacteria. Results The statistical resultsof 16S sequencing of intestinal microorganisms showed that the sequencing results of each sample were sufficient to re-flect the diversity contained in the current samples. All the intestinal microorganisms of the three diabetes model groupsshowed a significant decrease of Lactobacillus, but two of them showed an increase of the microorganism of Allobaculum.However, the recovery of Lactobacillus species was increased in the intestinal microorganisms of the diabetic mice treat-ed with metformin in three groups. Metformin treatment also transformed the abundance of Clostridium and Bacteroidesin the gut of diabetic mice to normal. Conclusion Metformin has certain effect on the intestinal flora of diabetic mice,and can promote the growth of Lactobacillus, which may be helpful for the treatment of diabetes.
      【Key words】 Diabetes; Intestinal flora; 16S high-throughput sequencing; Metformin; Lactobacillus