高脂饮食对菌群人源化小鼠肠道菌群结构的影响

Effect of High-fat Diet on the Structure of Gut Microbiota in Human Flora-associated Mice

采用高脂饮食建立肥胖菌群人源化(HFA)小鼠模型,研究高脂饮食对HFA小鼠肠道微生态结构的影响,探讨肥胖、饮食与肠道菌群之间的关系。将20只无菌小鼠接种健康人志愿者的粪便悬液构建HFA小鼠模型后分为普通组和高脂组,分别用基础饲料和高脂饲料饲喂8周,测定小鼠体质量、血糖血脂以及用PCR-DGGE方法检测肠道菌群的变化。结果显示:与普通组HFA小鼠相比,高脂组HFA小鼠体质量、肝质量、脂肪组织质量及血清中总甘油三酯水平显著增加(P<0.01),血糖水平也显著增加(P<0.05)。同时高脂组HFA小鼠肠道微生物多样性指数显著升高(P<0.05),正常优势菌群丰度降低,零时刻时的非优势菌群丰度增加,测序结果表明高脂饮食可能会诱导HFA小鼠肠道内Staphylococcus lentus、Staphylococcus vitulinus和Shigella flexneri等有害菌生长繁殖。本实验采用高脂饮食成功建立起肥胖HFA小鼠模型并证实了高脂饮食明显改变HFA小鼠肠道菌群结构。肠道菌群组成和细菌丰度发生很大变化导致肠道微生态失调,这提示人源性肠道菌群可能参与饮食结构失衡引起的肥胖的发展。

In order to explore the relationship among diet, obesity and intestinal microbiota, high-fat diet was used to establish obese human flora-associated （HFA） mouse model to investigate the effect of high fat diet on the structure of gut microbiota in HFA mice. Totally 20 pathogen-free mice were inoculated with fecal suspension derived from a healthy volunteer to obtain HFA mice. The HFA mice were fed a control or a high-fat diet for 8 weeks. Body weight, blood glucose and blood fat were determined and the change in gut microbiota was analyzed by PCR-DGGE. Results showed that body weight, liver weight, fat tissue weight and serum total triglyceride level revealed a significant increase （P 〈 0.01） in the high-fat group when compared with the control group. Blood glucose level also increased significantly （P 〈 0.05） in highfat diet-fed HFA mice. The gut bacterial diversity index of the high-fat group significantly increased （P 〈 0.05）. The abundance of the dominant bacteria at zero time reduced, but the abundance of bacteria that were not dominant at zero time increased. DNA sequencing showed that high-fat diet may induce Staphylococcus lentus, Staphylococcus vitulinus and Shigella flexneri to bloom in the gut of HFA mice. An obese HFA mouse model was successfully established by feeding a high-fat diet and high-fat diet obviously altered the structure of gut microbiota in HFA mice. The composition and bacterial abundance of intestinal flora in high-fat diet-feed HFA mice greatly changed, leading to intestinal dysbacteriosis. It suggests that human-derived intestinal flora may be involved in the development of obesity caused by imbalanced dietary profile.