肠道细菌Phascolarctobacterium/Phascolarctobacterium faecium与2型糖尿病中代谢紊乱的关联分析  

Correlation between intestinal bacteria Phascolarctobacterium/Phascolarctobacterium faecium and metabolic disorder in patients with type 2 diabetes mellitus

作　　者：李莉莎 熊大迁[1] LI Lisha;XIONG Daqian(Department of Clinical Laboratory,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan Province,610072,China)

机构地区：[1]成都中医药大学附属医院检验科,成都610072

出　　处：《陆军军医大学学报》2024年第13期1561-1568,共8页Journal of Army Medical University

基　　金：四川省科技计划项目重点研发项目(2020YFS0375);成都中医药大学杏林学者项目-苗圃人才专项(MPRC2023025)。

摘　　要：目的寻找新发2型糖尿病(type 2 diabetes mellitus,T2DM)中的差异菌群,并初步评估差异核心菌群在疾病代谢紊乱中的重要作用。方法选取2020年9-11月在成都中医药大学附属医院内分泌科就诊的30名T2DM患者与体检中心的30名健康者为研究对象,构成T2DM组与对照组(NC组)。收集2组志愿者的血液标本和粪便标本,血液标本用于葡萄糖、胰岛素和血脂类指标的检测,粪便标本用于肠道菌群的16SrRNA检测,之后结合生物信息学分析、Pearson相关性分析等统计学方法,对不同组间的T2DM血液指标和差异菌种进行分析;使用RT-qPCR验证前期小RNA谱筛选结果,并将筛选的差异菌与早期实验的脂质代谢组、miRNAs谱基因组数据进行多组学关联分析,构建多参数的ROC曲线模型。结果T2DM具有特异性的肠道菌群特征,考拉杆菌属(Phascolarctobacterium)与粪考拉杆菌(Phascolarctobacterium faecium,P.faecium)在患病前后差异具有统计学意义。Pearson相关性分析提示,P.faecium与高密度脂蛋白(high-density lipoprotein,HDL)(r=-0.78,P<0.001)、低密度脂蛋白(low-density lipoprotein,LDL)(r=-0.89,P<0.001)、胰岛素(r=-0.71,P<0.01)具有较强的负相关性。Phascolarctobacterium则与胰岛素(r=-0.67,P<0.001)、体质量指数(body mass index,BMI)(r=-0.64,P<0.001)具有一定的负相关性,所构建的基于Phascolarctobacterium/P.faecium、脂肪酸α-linolenic acid、miR-122-5p的联合指标的ROC曲线模型,能够比较准确地将T2DM患者与健康者区分,曲线下面积(area under curve,AUC)分别为0.928(P=0.001)与0.934(P<0.001)。结论T2DM患者具有特异性的肠道菌群分布,其中,Phascolarctobacterium菌属和P.faecium菌与疾病的代谢紊乱密切相关,两类细菌理论上可作为T2DM的核心菌。Objective To explore the differential microbiota in patients with newly diagnosed type 2 diabetes mellitus(T2DM),and to preliminarily evaluate the importance of the differential core microbiota in the metabolic disorder.Methods A total of 30 T2DM patients who were treated at the Endocrinology Department of our hospital from September to November 2020,and 30 healthy individuals taking physical examination during the same period were enrolled and assigned into the T2DM group and the control group,respectively.Their blood and fecal samples were collected for the detection of glucose,insulin,and lipid indicators levels and for gut microbiota using 16SrRNA,respectively.Subsequently,bioinformatics analysis,Pearson correlation analysis,and other statistical methods were applied to analyze the differences in T2DM blood indicators and specific bacterial species between the 2 groups.RT-qPCR was used to verify the screening results of small RNA profiles.Then a multi-parameter receiver operating characteristic(ROC)curve model was constructed based on the results of correlation analysis including microbiome,lipid metabolome and miRNAs spectrum genomic detection data of early research.Results T2DM showed specific characteristics of intestinal microbiota,with Phascolarctobacterium and Phascolarctobacterium.faecium(P.faecium)showing significant differences before and after the onset of the disease.Pearson correlation analysis suggested that P.faecium was negatively correlated with high-density lipoprotein(HDL)(r=-0.78,P<0.001),low-density lipoprotein(LDL)(r=-0.89,P<0.001),and insulin(r=-0.71,P<0.001).While,Phascolarctobacterium was negatively correlated with insulin(r=-0.67,P<0.001)and body mass index(BMI)(r=-0.64,P<0.001).The ROC curve model based on Phascolarctobacterium/P.faecium,α-linolenic acid,and miR-122-5p could accurately distinguish between T2DM patients and healthy individuals,with a value of area under the curve of 0.928(P=0.0001)and 0.934(P<0.0001),which suggesting core values of 2 types of bacteria in the disease.

关 键 词：2型糖尿病 考拉杆菌属 粪考拉杆菌 多组学联合分析 

分 类 号：R364.2[医药卫生—病理学] R378.2[医药卫生—基础医学] R587.1