摘要
目的肠道菌群的改变与代谢性疾病密切相关。文章旨在分析抗生素对小鼠糖代谢及肠道菌群的影响,并进一步探讨肠道菌群在广谱抗生素降低db/db糖尿病小鼠血糖中的作用机制。方法将16只C57BL/KsJ-db/db小鼠随机数字表法分为抗生素组和对照组,每组8只。抗生素组:以广谱抗生素[万古霉素10mg/(kg·d)、羧苄青霉素50mg/(kg·d)、甲硝唑50mg/(kg·d)、新霉素30mg/(kg·d)]处理;对照组:以1%纤维素钠溶液作安慰剂处理。每周记录1次小鼠的空腹血糖和体重,同时取小鼠粪便做16SrDNA基因测序分析,比较实验前后两组小鼠空腹血糖、体重、肠道菌群相对丰度、香浓指数(Shannon)、辛普森指数(Simpson)以及胰高血糖素样肽-1(GLP-1)的变化。结果治疗5周后,抗生素组可显著降低d小鼠空腹血糖水平[(9.59±4.49)mmol/Lvs(19.71±8.74)mmol/L,P=0.016]。抗生素组变形杆菌(Proteobacteria)的相对丰度(0.471±0.12)较对照组(0.177±0.12)明显升高(P<0.05)。与对照组相比,经抗生素处理的db/db小鼠显著改变了多个OTU聚类,抗生素组变形杆菌门、肠杆菌科、γ-变形杆菌纲、肠杆菌目显著增多。抗生素组较对照组肠道菌群Shannon指数显著下降(3.135vs5.359,P<0.01),Simpson指数亦下降(0.794vs0.946,P<0.01)。结论广谱抗生素可以显著降低db/db糖尿病小鼠的空腹血糖水平,降低肠道菌群多样性,且小鼠肠道菌群的改变可能在广谱抗生素降低血糖的过程中起重要作用。
Objective The alterations of gut microbiota is closely related to metabolic diseases. The aim of this study was to analyze the effects of antibiotics on glucose metabolism and gut microbiota in mice, and to further explore the mechanism of gut microbiota in reducing blood glucose in db/db diabetic mice by broad-spectrum antibiotics. Methods 16 C57BL/KsJ-db/db mice were randomly divided into antibiotic group and control group with 8 mice in each group. Antibiotic group: broad-spectrum antibiotics(vancomycin 10mg/(kg·d), carbenicillin 50mg/(kg·d), metronidazole 50mg/(kg·d), neomycin 30mg/(kg·d));Control group: 1% cellulose sodium solution as placebo treatment. Fasting blood glucose and body weights were recorded once a week during the study. At the same time, feces were collected for 16S rDNA gene sequencing analysis. The changes of fasting blood glucose, body weight, the relative abundance of microbiota, Shannon index, Simpson index and GLP-1 were compared between the two groups. Results After 5 weeks of treatment with broad-spectrum antibiotics (Vancomycin , Carbenicillin , Metronidazole , and Neomycin ), fasting blood glucose levels in db/db diabetic mice were significantly decreased (9.59±4.49mmol/L vs 19.71±8.74mmol/L,P=0.016). At the same time, antibiotics can also affect the gut microbiota of mice. The relative abundance of Proteobacteria in mice treated with antibiotics was significantly higher than that in control group (0.471±0.12 vs 0.177±0.12, P<0.05), and the OTUs of Proteobacteria, Enterobacteriaceae, Gamma-proteobacteria, and Enterobacteriales increased in mice treated with antibiotics compared with controls. In addition, we also showed antibiotics could change the diversity of gut microbiota, and the diversity of gut microbiota in antibiotic treated mice decreased significantly (Shannon index 3.135 vs 5.359, P<0.01);Simpson index 0.794 vs 0.946, P<0.01). Conclusion Broad-spectrum antibiotics can significantly reduce the fasting blood glucose level and the diversity of gut microbiota of db /
作者
郑舟琴
王瑞风
陈俊秀
孙中帅
臧璞
杜宏
ZHENG Zhou-qin;WANG Rui-feng;CHEN Jun-xiu;SUN Zhong-shuai;ZANG Pu;DU Hong(Department of Endocrinology,Nanjing Clinical Institute of Southern Medical University/General Hospital of Eastern Theater Command,PLA,Nanjing 210002,Jiangsu,China)
出处
《医学研究生学报》
CAS
北大核心
2019年第7期678-683,共6页
Journal of Medical Postgraduates
基金
国家自然科学基金(81173622)
关键词
肠道菌群
广谱抗生素
血糖
糖尿病
gut microbiota
broad-spectrum antibiotics
blood glucose
diabetes