胰岛素抵抗小鼠肠道菌群与FGF21的相关性研究

Correlation between gut microbiota and FGF21 in mice with insulin resistance

目的研究糖耐量正常人粪菌液移植(fecal bacteria transplantation,FMT)对胰岛素抵抗(insulin resistance,IR)小鼠肠道菌群的影响及其与成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)的相关性,探究肠道菌群影响IR的可能机制。方法采用高脂饮食建立IR模型,筛选30只建模成功的小鼠随机分成3组:IR组、IR+二甲双胍(Met)组、IR+粪菌液移植(FMT)组,及空白对照(Control)组,每组10只。给药8周,记录第8周小鼠的体质量、空腹血糖;采用RT-qPCR检测粪样中靶标菌的数量,肝脏、结肠、回肠中FGF21及其受体mRNA表达水平。结果①与Control组比较,IR组小鼠体质量和空腹血糖升高,肝脏、结肠和回肠中FGF21/β-Klotho/FGFR1/FGFR4 mRNA表达降低,粪样中Bacteroides、B.sartorii降低,P.distasonis、M.schaedleri、R.gnavus升高,Met、FMT干预后上述指标均逆转。②FGF21的表达与FBG、P.distasonis、M.schaedleri、R.gnavus呈负相关,与Bacteroides、B.sartorii呈正相关。结论FMT可增加FGF21的表达量和调节肠道菌群,且二者密切相关,可能是FMT改善胰岛素抵抗的重要机制之一。

Aim To study the effect of normal glucose tolerance fecal microbiota transplantation(FMT)on the gut microbiota in mice with insulin resistance(IR)and its correlation with FGF21,and to explore the possible mechanisms of gut microbiota affecting IR.Methods After the establishment of IR model with high-fat diet feeding,30 successful IR model mice were randomly divided into three groups:insulin resistance(IR)group,IR+metformin(Met)group,and IR+glucose tolerance normal fecal microbiota transplantation(FMT)group,and blank control(Control)group,with 10 mice in each group.After eight weeks of administration,the body mass and fasting blood glucose of mice at 8th week were recorded,then the number of target bacteria in fecal samples and the mRNA expression levels of FGF21 and its receptors in liver,colon and ileum tissues were detected by Real-time quantitative PCR(RT-qPCR).Results①Compared with control group,the body mass and fasting blood glucose increased in IR group mice,while the mRNA expression levels of FGF21/β-Klotho/FGFR1/FGFR4 in liver,colon and ileum tissues were down-regulated.The levels of Bacteroides and B.sartorii were reduced in fecal samples,and the levels of P.distasonis,M.schaedleri and R.gnavus increased.These indices were reverted by Met and FMT treatment.②The expression of FGF21 was negatively correlated with FBG,P.distasonis,M.schaedleri and R.gnavus,and positively correlated with Bacteroides and B.sartorii.Conclusions FMT can increase the expression level of FGF21 and regulate gut microbiota,and the two are closely related,which may be one of the important mechanisms of FMT in improving insulin resistance.