糖脂代谢性疾病模型小鼠肠道菌群特征分析  

Characteristics of gut microbiota in mouse models of glucose and lipid metabolism diseases

作　　者：杨玲 方钊妍 殷怡帆 罗朵生 YANG Ling;FANG Zhao-yan;YIN Yi-fan;LUO Duo-sheng(Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine,Guangdong Pharmaceutical University,Guangzhou,Guangdong 510006,China;Key Laboratory of Prevention and Treatment of Metabolic Diseases uuith Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou,Guangdong 510006,China;不详)

机构地区：[1]广东省代谢病中西医结合研究中心 [2]广东省代谢性疾病中医药防治重点实验室广东药科大学,广东广州510006

出　　处：《中国微生态学杂志》2022年第5期497-504,共8页Chinese Journal of Microecology

基　　金：国家自然科学基金(81830113);广东省自然科学基金(2020A1515010245)。

摘　　要：目的基于16S rDNA测序研究非酒精性脂肪性肝病(NAFLD)、2型糖尿病(T2D)及动脉粥样硬化(AS)小鼠的肠道菌群特征,分析上述疾病肠道微生物的异同。方法以SPF级C57BL/6J雄鼠为对象,分别采用高脂饮食制备NAFLD模型,高脂饮食联合小剂量链脲佐菌素腹腔注射建立T2D模型,ApoE;小鼠高脂饮食诱导AS模型,另设对照组,每组10只。采用试剂盒测定小鼠血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)的水平。收集粪便样本,以Illumina MiSeq测序平台,采用QIIME2软件对肠道菌群的可分类操作单元(OTUs)数量,Alpha、Beta多样性和菌群多样性指数以及差异菌门、菌属等进行综合分析与评价,并对肠道菌群代谢功能进行预测。结果与对照组小鼠比,T2D组、NAFLD组、AS组血清中TC、TG和LDL-C水平均显著升高,菌群多样性指数显著降低(F=14.33,P<0.01),Firmicutes/Bacteroidetes比值逐渐升高;双歧杆菌属(Bifidobacterium)丰度在AS组、T2D组中显著增加(F=12.15,P<0.01),在NAFLD组中显著下降(F=12.15,P<0.05),乳杆菌属(Lactobacillus)丰度在NAFLD组、AS组中著降低(F=9.35,P<0.01),在T2D组中显著降低。关联分析表明Lactobacillus、Akkermansia等与血脂呈负相关,Faecalibaculum、Blautia等与血脂呈正相关。肠道菌群参与代谢性疾病主要涉及碳水化合物代谢、氨基酸代谢、脂质代谢以及能量代谢等通路。结论本研究阐明了NAFLD、T2D、AS肠道微生物组成与变化的共性和个性特征,为靶向调控肠道微生物治疗代谢性疾病提供科学依据。Objective To observe the characteristics of gut microbiota in mouse models of nonalcoholic fatty liver disease(NAFLD),type 2 diabetes(T2 D)and atherosclerosis(AS)based on 16 S rDNA sequencing technology.Methods C57 BL/6 J and ApoE;male mice were used to respectively establish the NAFLD models(induced by high-fat diet)and T2 D models(induced by high-fat diet combined with streptozotocin);ApoE;mice were fed high-fat diet to establish the AS models.The control group was fed with normal diet,ten animals in each group.The contents of total cholesterol(TC),triglyceride(TG)and low-density lipoprotein(LDL-C)in serum were determined.The feces were collected,and the number of gut microbiota taxa(OTUs),alpha and beta diversities,and diversity index were comprehensively analyzed and evaluated based on Illumina MiSeq sequencing with QIIME2 software.The metabolic function of intestinal microbiota was also predicted.Results Compared with the control group,the contents of TC,TG and LDL-C in the T2 D,NAFLD and AS groups significantly increased,while the diversity indexes decreased(F=14.33,P<0.01);Firmicutes/Bacteroidetes gradually increased.The abundance of Bifidobacterium dramatically increased in AS and T2 D groups(F=12.15,P<0.01),while decreased in NAFLD group(F=12.15,P<0.05).The abundance of Lactobacillus significantly reduced in NAFLD and AS groups(F=9.35,P<0.01),while increased in T2 D group.Association analysis showed that Lactobacillus and Akkermansia were negatively correlated with TC,TG and LDL-C,but positively correlated with Faecalibaculum and Blautia.The pathways associated with intestinal microbiota in metabolic diseases mainly involved carbohydrate metabolism,amino acid metabolism,lipid metabolism,and energy metabolism.Conclusion We clarified the common and special characteristics of gut microbiota in NAFLD,T2 D and AS,which may provide a scientific basis for the targeted regulation of gut microbes for treatment of metabolic diseases.

关 键 词：肠道菌群 2型糖尿病 动脉粥样硬化 非酒精性脂肪性肝病 

分 类 号：R589[医药卫生—内分泌]