冠状动脉粥样硬化性心脏病患者肠道菌群丰度与血脂和血尿酸水平的相关性

Correlation between gut flora abundance and blood lipid,blood uric acid levels in patients with coronary atherosclerotic heart disease

目的 探讨冠状动脉粥样硬化性心脏病(CAHD)患者肠道菌群丰度与血脂、血尿酸水平的相关性。方法 选取2016年9月至2017年11月新乡医学院第一附属医院心血管内科收治的疑似CAHD进行冠状动脉造影患者106例为研究对象,根据冠状动脉造影结果分为CAHD组(n=68)和非CAHD组(对照组,n=38),均于入院次日清晨空腹抽取肘静脉血,检测血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、血尿酸(UA)水平;并于治疗前收集2组受试者新鲜粪便样本5g,参照粪便样本DNA提取试剂盒方法提取粪便样本DNA,采用Illumina MiSeq平台实施高通量测序,检测受试者肠道菌群丰度,对肠道菌群丰度与血脂、血尿酸水平进行相关性分析。结果 与对照组受试者比较,CAHD组受试者的血清UA、TC、LDL水平显著升高,HDL水平显著降低(P<0.05)。2组受试者肠道菌群共检测到8个菌门,其中拟杆菌门、厚壁菌门、变形菌门、放线菌门的检出率均为100%,梭杆菌门、软壁菌门、互养菌门、广古菌门检出率比较差异均无统计学意义(χ^2=0.009、0.000、0.000、0.000,P>0.05);与对照组受试者比较,CAHD组拟杆菌门细菌丰度减小(P<0.05),厚壁菌门细菌丰度增加(P<0.05)。CAHD组受试者β-变形菌纲细菌丰度小于对照组受试者(P<0.05),梭菌纲细菌丰度大于对照组(P<0.05),2组受试者β-变形菌纲、梭菌纲细菌检出率均为100%。CAHD组受试者拟杆菌目、Burkholderiales目、双歧杆菌目、乳酸杆菌目细菌丰度小于对照组(P<0.05),2组受试者拟杆菌目、Burkholderiales目、双歧杆菌目、乳酸杆菌目细菌检出率均为100%。CAHD组受试者消化链球菌科、Erysipelotrichaceae科细菌丰度大于对照组(P<0.05),2组受试者消化链球菌科、Erysipelotrichaceae科细菌检出率均为100%。CAHD组受试者拟杆菌属、Roseburia属、乳酸杆菌属、双歧杆菌属细菌丰度小于对照组(P<0.05),Blautia属、Odoribacter属、Ruminococcus-2属、Faecalibacterium属、Alistipes属、Subdoligranulum属、埃希氏菌属、Stercoris种细菌丰度大于对照组(P<0.05);CAHD组受试者Odoribacter属、Alistipe属细菌检出率小于对照组(χ^2=3.892、8.853,P<0.05)。2组受试者血UA水平与双歧杆菌目、乳酸杆菌属细菌丰度呈负相关(r=-0.562、-0.112、-0.429、-0.045,P<0.05),与埃希氏菌属细菌丰度成正相关(r=0.781、0.193,P<0.05);CAHD组受试者血UA水平与Burkholderiales目细菌丰度呈正相关(r=0.716,P<0.05),与乳酸杆菌目细菌丰度呈负相关(r=-0.687,P<0.05)。2组受试者血TG水平与拟杆菌目、Odoribacter属细菌丰度呈负相关(r=-0.761、-0.354、-0.323、-0.256,P<0.05),与梭菌纲细菌丰度呈正相关(r=0.867、0.447,P<0.05);CAHD组受试者血TG水平与Stercoris种细菌丰度呈正相关(r=0.258,P<0.05)。2组受试者血HDL水平与消化链球菌科、梭菌纲细菌丰度呈正相关(r=0.650、0.146、0.597、0.012,P<0.05);CAHD组受试者血HDL水平与软壁菌门细菌丰度呈正相关(r=0.656,P<0.05)。2组受试者血LDL水平与消化链球菌科、梭菌纲细菌丰度均呈负相关(r=-0.497、-0.036、-0.839、-0.181,P<0.05)。结论 CAHD受试者与对照组的肠道菌群丰度在门、纲、目、科、属、种水平存在一定差异;肠道菌群丰度与CAHD患者的血脂、血尿酸水平相关。

Objective To explore the correlation between the gut flora abundance and blood lipid,blood uric acid (UA) levels in patients with coronary atherosclerotic heart disease (CAHD).Methods One hundred and six suspected CAHD patients who underwent coronary arteringraphy in the First Affiliated Hospital of Xinxiang Medical University from September 2016 to November 2017 were selected as the study objects.The patients were divided into CAHD group (n=68) and non-CAHD group (control group)(n=38) according to the results of coronary angiography.The fasting elbow venous blood of all patients were taken on the next morning after admission to detect the total cholesterol (TC),triglyceride (TG),low density lipoprotein (LDL),high density lipoprotein (HDL) and UA levels.Fresh fecal samples (5 g)were collected from the patients of the two groups before treatment.The fecal sample DNA was extracted according to the method of the fecal sample DNA extraction kit.High-throughput sequencing was performed by using the Illumina MiSeq platform to detect the intestinal flora abundance.The correlation between intestinal flora abundance and blood lipid,UA levels was analyzed.Results Compared with the control group,the serum levels of UA,TC and LDL of patients in the CAHD group increased significantly,while the serum levels of HDL decreased significantly (P<0.05).A total of eight bacterium phylum were detected in the two groups.Among them,the detection rates of Bacteroidetes,Tenericumtes,Synergistetes and Actinobacteria were 100%;there was no statistic difference in the detection rates of Acidobacteria,Tendericutes,Synergistetes,Euryarchaeota between the two groups (χ^2=0.009,0.000,0.000,0.000;P>0.05).Compared with the control group,the abundance of Bacteroidetes of patients in the CAHD group decreased and the abundance of Firmicutes increased (P<0.05).The abundance of β-aproteobacteria of patients in the CAHD group was less than that in the control group (P<0.05),and the abundance of Clostridia was more than that in the control group (P<0.05).The detection rates of β-aproteobacteria and Clostridium were 100% in the both groups.The abundance of Bacteroidales,Burkholderiales,Bifidobacteriales,Lactobacillales in CAHD group was lower than that in the control group (P<0.05),and the detection rates of them were 100% in the two groups.The abundance of Peptostreptococcace and Erysipelotrichaceae in CAHD group was higher than that in control group (P<0.05) and the detection rates of them were 100% in the two groups.The abundance of Bacteroide,Roseburia,Lactobacilleae and Bifidobacterium in CAHD group was less than that in the control group(P<0.05);the abundance of Blautia,Odoribacter,Ruminococcus-2,Faecalibacterium,Alistipes,Subdoligranulum and Escherichiacoli in CAHD group was more than that in the control group(P<0.05).The detection rates of Odoribacter,Alistipe in CAHD group was lower than those in the control group(χ 2=3.892,8.853;P<0.05).The blood UA levels were negatively correlated with the abundance of Bifidobacteriales and Latobacillus (r=-0.562,-0.112,-0.429,-0.045;P<0.05),and were positively correlated with the abundance of Escherichia (r=0.718,0.193;P<0.05) in the two groups.The blood UA levels were positively correlated with the abundance of Burkholderiales (r=0.716,P<0.05),and were negatively correlated with the abundance of Lactobacillales (r=-0.687,P<0.05) in the CAHD group.The serum levels of TG were negatively correlated with the abundance of Bacteroidales and Odoribacter (r=-0.761,-0.354,-0.323,-0.256;P<0.05),and were positively correlated with the abundance of Clostridia (r=0.867,0.447;P<0.05) in the two groups.The serum levels of TG were positively correlated with the abundance of Stercoris (r=0.258,P<0.05).The serum levels of HDL were positively correlated with the abundance of Peptostreptococcace and Clostridia (r=0.650,0.146,0.597,0.012;P<0.05) in the two groups.The serum levels of HDL were positively correlated with the abundance of Tendericutes (r=0.656,P<0.05) in the CAHD group.The serum levels of HDL were negatively correlated with the abundance of Peptostreptococcaceae and Clostridia (r=-0.497,-0.036,-0.839,0.181;P<0.05) in the two groups.Conclusion The abundance of gut flora in CAHD group and control group is different in the level of phylum,class,order,family,genus and species.The abundance of gut flora was related to the blood lipid and blood UA level in patients with CAHD.