摘要
目的 研究2型糖尿病(T2DM)粪菌液对正常饮食和高脂饮食小鼠肠道菌群的影响,并分析肠道菌群与血糖血脂的相关性.方法 40只雄性C57BL/6小鼠随机分为正常饮食组(ND组)、菌群移植组(MT组)、高脂饮食组(HFD组)与HFD+MT组,每组10只,T2DM人粪菌液干预8周.采用RT-qPCR测定粪便中多形拟杆菌、狄氏副拟杆菌、嗜黏蛋白阿克曼菌、普拉梭菌、嗜酸乳杆菌、大肠埃希菌数量,并分析菌群与餐后血糖(PPG)、空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、体重和炎症指标的相关性.结果 四组小鼠粪便样本中大肠埃希菌、普拉梭菌、嗜酸乳杆菌相对丰度存在显著差异(F=8.081,P＜001;F=17.353,P＜001;F=7.181,P＜001).与ND组比,MT、HFD、HFD+MT组大肠埃希菌水平升高,普拉梭菌及嗜酸乳杆菌水平降低.与HFD组比较,HFD+MT组大肠埃希菌升高,普拉梭菌降低.普拉梭菌与PPG、FBG、TC、脂多糖结合蛋白(LBP)显著相关(r=-0.585,r=-0.639,r=-0.716,r=-0.626,均P＜0.05),大肠埃希菌与PPG、FBG、TC、肿瘤坏死因子α(TNF-α)、LBP显著相关(r=0.455,r=0.545,r=0.456,r=0.451,r=0.433,均P＜0.05),嗜酸乳杆菌与 FBG、TC、TNF-α、LBP 显著负相关(r=-0.583,r=-0.497,r=-0.565,r=-0.614,均P＜0.05).结论 T2DM人粪菌移植可能通过改变正常饮食或高脂饮食小鼠大肠埃希菌、普拉梭菌及嗜酸乳杆菌水平,使肠道菌群失衡,引起炎症,进而导致糖脂代谢紊乱.
Abstract
Objective To explore the effect of type 2 diabetes(T2DM)fecal bacteria on intestinal flora of normal and high-fat diet mice,and analyze the correlation of intestinal flora with blood glucose,lipid and inflammation.Methods Forty male C57BL/6 mice were randomly divided into four groups:the normal diet(ND)group,the microbiota transplantation(MT)group,the high-fat diet(HFD)group,and the HFD+MT group,with 10 mice in each group.These mice underwent an 8-week intervention with human fecal microbiota from T2DM patients.The copies of Bacteroides thet-aiotaomicron,Parabacteroides distasonis,Akkermansia muciniphila,Faecalibacterium prausnitzii,Lactobacillus acido-philus and Escherichia coli in fecal samples were measured by RT-qPCR.The correlations between these species and post-prandial glucose(PPG),fasting blood glucose(FBG),total cholesterol(TC),triglycerides(TG)and inflammatory indices were analyzed.Results Significant differences in the relative abundances of E.coli,F.prausnitzii and L.acidophilus were observed among the four groups(F=8.081,P＜001;F=17.353,P＜001;F=7.181,P＜001).Compared with the ND group,the MT group,HFD group and HFD+MT group showed increased level of E.coli and decreased levels of F.praus-nitzii and L.acidophilus.Comparing with the HFD group and the HFD+MT group,the latter exhibited higher level of E.coli and lower level of F.prausnitzii.Notably,F.prausnitzii was significantly correlated with PPG,FBG,TC and LBP(r=-0.585,r=-0.639,r=-0.716,r=-0.626;all P＜0.05).E.coli demonstrated significant correlations with PPG,FBG,TC,TNF-α and LBP(r=0.455,r=0.545,r=0.456,r=0.451,r=0.433;all P＜0.05).Conversely,L.acidophilus showed signific-ant negative correlations with FBG,TC,TNF-α and LBP(r=-0.583,r=-0.497,r=-0.565,r=-0.614;all P＜0.05).Conclusion Fecal microbiota from patients with T2DM may disrupt the balance of intestinal microbiota in mice with normal or high-fat diets by altering the levels of E.coli,F.prausnitzii and L.acidophilus,inducing inflammation and sub-sequently causing glucose and lipid metabolism disorders.
基金项目
国家自然科学基金地区项目(82360728)
陕西省重点产业创新链项目(2019ZDLSF04-02)
安康市科学技术研究发展计划项目(AK2023-SF-04)
维普
万方数据