长期抗生素暴露对高脂饮食负荷小鼠糖代谢和肠道菌群的影响

目的 探究长期抗生素暴露对高脂饮食负荷小鼠糖代谢和肠道菌群的影响。方法 45只新生BALB/c小鼠随机分为对照组、高脂饮食组和高脂饮食抗生素联合组（n=15），联合组小鼠出生后以头孢曲松（100mg/kg）灌胃15周，第21d起，高脂组和联合组以高脂饲料，对照组以普通饲料喂养12周。实验结束后，对小鼠进行口服糖耐量实验并采集小鼠内脏、脂肪、血清和粪便，测定小鼠脏器系数、脂体比、血糖、胰岛素和瘦素及肠道菌群。结果 高脂饮食引起小鼠肝脏系数、总脂体比、胰岛素抵抗指数、空腹血糖和血糖曲线下面积显著升高（P均<0.05）。与对照组和高脂组比较，联合组alpha多样性指数显著降低（P<0.05）；主坐标分析显示三组组间群落组成具有明显差异。门水平上，与高脂组比较，联合组厚壁菌门相对丰度显著升高（P<0.05），拟杆菌门相对丰度显著降低（P<0.05），高脂组变形菌门相对丰度显著高于对照组和联合组（P均<0.05）。属水平上，高脂饮食诱导厚壁菌门布劳特氏菌属（Blautia）相对丰度增加，降低了拟杆菌门另枝菌属（Alistipes）相对丰度，联合组厚壁菌门肠球菌属（Enterococcus）和葡萄球菌属（Staphylococcus）相对丰度明显升高，其他菌属相对丰度均降低。结论 长期抗生素暴露可能通过改变肠道中细菌生长从而调节肠道菌群，在一定程度上抵抗高脂饮食负荷小鼠的糖代谢失调，表明肠道细菌和宿主代谢功能间存在密切的关联，肠道细菌有望成为改善膳食营养调节的机体能量代谢的重要靶点。

Effects of long-term antibiotic exposure on glucose metabolism and intestinal microbiota of high-fat diet mice

To explore the effects of long-term antibiotic exposure on glucose metabolism and intestinal microbiota of high-fat diet mice. Methods 45 newborn BALB/c mice were randomly divided into control group, high-fat diet group, and high-fat diet combined with antibiotic group(n=15, respectively). The mice in the combination group were given ceftriaxone(100 mg/kg) by gavage from birth to postnatal 15 weeks. From the 21 st day, the high-fat group and the combination group were fed with high-fat diet and the control group was fed with common diet for 12 weeks each. After the experiment, the mice were subjected to oral glucose tolerance test, and the serum and feces were collected to determine the blood glucose, insulin and leptin levels and intestinal microbiota of the mice. Additional, the viscera and fat were collected for organ coefficient and fat-body ratio, respectively. Results The liver coefficient, total fat-body ratio, HOMA-IR index, FBG and AUC of blood glucose in mice were significantly increased due to high-fat diet(P<0.05, respectively). Compared with the control group and the high-fat group, the alpha diversity of the combination group was significantly reduced(P<0.05). PCoA analysis showed that the community composition of the three groups was significantly different. At the phylum level, compared with the high-fat diet group, the combination group showed a significantly increase in the relative abundance of Firmicutes and a decrease in the relative abundance of Bacteroides(P<0.05), and the relative abundance of Proteobacteria in the high-fat diet group was higher than that of the control and combination groups(P<0.05, respectively). At the genus level, high-fat diet induced an increase in the relative abundance of Blauti and a decrease in the relative abundance of Alistipes. The relative abundances of Enterococcus and Staphylococcus were significantly increased, while the relative abundance of other bacterial genera decreased. Conclusion Long-term antibiotic exposure may regulate the intestinal microbiota by inhibiting the growth of microbes in the intestines, by which ameliorates the glucose metabolism dysfunction in high-fat diet mice. These results, again, suggest the close relationship between intestinal microbiota and metabolism, indicating that intestinal microbiota may be a important target in the management of metabolism though diet nutrition.