高脂饮食诱导的肥胖及肥胖抵抗小鼠肠道菌群元基因组的比较研究

Comparison of the gut microbiome metagenome in diet-induced obesity mice and diet-induced obesity resistant mice

目的比较高脂饮食诱导肥胖(DIO)小鼠及高脂饮食诱导肥胖抵抗(DIO-R)小鼠肠道菌群元基因组的差异。方法将40只C57BL/6J雄性小鼠适应性饲养2周后,随机分为正常组(10只)和高脂饮食造模组(30只),分别给予普通饮食和高脂饮食。造模8周后,按体重增量的不同,将高脂饮食组小鼠又分为肥胖组(DIO组,22只)和肥胖抵抗组(DIO-R组,8只)。搜集并提取3组小鼠粪便样本菌群基因组,采用Illumina公司的Hiseq2000分析样本的肠道宏基因组功能及物种组成。结果 DIO组小鼠肠道菌群在执行多糖代谢、氨基酸代谢、基因信息翻译、信号转导、细胞能动性多种功能的基因数与DIO-R组有差异,其余同DIO-R组无明显差异;两组的多项代谢功能及基因信息处理所对应的基因数均明显低于正常组。DIO组小鼠肠道变形杆菌门的相对含量百分比较正常组及DIO-R组显著增高;厚壁菌门的含量较DIO-R组升高,类杆菌门的含量则显著下降,类杆菌/厚壁菌的比值较DIO-R组明显下降;DIO-R组除变形杆菌门的含量低于正常组外,其余两组无明显差异。结论 DIO及DIO-R小鼠肠道菌群元基因组中的肠道菌群功能存在差异;DIO小鼠肠道菌群门级别与DIO-R小鼠有显著差异,两者与正常组相比,都处于代谢紊乱状态。

Objective To study the differences of the gut microbiome metagenome in high-fat-diet-induced obesity （DIO） mice and DIO resistant （DIO-R） mice. Methods Forty male C57BL/fJ mice were fed adaptively for two weeks and then were randomized into normal control group （10 mice） fed with common feed and model group （30 mice） fed with high-fat diet. Eight weeks later, mice in the high-fat diet group were subdivided into DIO group （22 mice） and DIO-R group （8 mice）. Feces samples from DIO, DIO-R, and normal groups were collected, and the total DNA was extracted immediately. The intestinal metagenome of three samples was sequenced and analyzed by Hiseq2000 （Illumina Co., Ltd.）. Results Different numbers of genes involved in glucose metabolism, amino acid metabolism, gene information translation, signal transduction and cell motility were observed in DIO group and DIO-R group. Compared with those in control group, genes of several metabolic functions and gene information processing had significantly low expression in DIO mice. The quantity of intestinal proteobacteria in DIO mice was higher than that in normal group and DIO-R group~ the quantity of intestinal firmicutes in DIO-R mice was higher than that in control group. Bacteroides/firmicutes ratio was decreased significantly in DIO-R group. Except for the markedly low amount of proteobacteria, no difference was found between DIO-R and normal groups. Conclusion Marked discrepancies were displayed between the gut microbiomes in DIO mice and DIO-R mice. Abnormal gut microbiomes were found in both DIO and DIO-R mice, suggesting different metabolic disorders in these groups compared with normal group.