藏族人群动脉粥样硬化性心血管疾病10年发病风险肠道微生物特征研究  

Study on intestinal microbial characteristics of 10-year risk of atherosclerotic cardiovascular disease in Tibetan population

作　　者：向哲军 窦青瑜[2] 赵星 杨淑娟 曾沛斌 XIANG Zhe-ju;DOU Qing-yu;ZHAO Xing;YANG Shu-juan;ZENG Pei-bin(West China School of Public Health,Sichuan University/West China Fourth Hospital,Sichuan University,Chengdu,Sichuan 610041,China;不详)

机构地区：[1]四川大学华西公共卫生学院/华西第四医院,四川成都610041 [2]四川大学华西医院国家老年疾病临床医学研究中心

出　　处：《现代预防医学》2024年第11期1921-1927,1943,共8页Modern Preventive Medicine

基　　金：国家重点研发计划(2020YFC2008005,2023YFC3604702,2017YFC0907305);四川省区域创新合作项目(2021YFQ0031);成都市技术创新研发项目(2021-YF05-00886-SN);成都市科技局项目(2022-YF05-0640-SN)。

摘　　要：目的探究藏族地区人群不同动脉粥样硬化性心血管疾病(ASCVD)10年发病风险人群的肠道菌群及其代谢通路和功能基因的差异。方法基于西南区域自然人群队列拉萨地区的随访调查数据,参照《中国血脂管理指南2023》总共纳入94人进行后续分析。对样本粪便提取DNA后进行宏基因组测序分析,通过生物信息学方法,比较不同ASCVD10年发生风险人群的肠道菌群构成。并利用京都基因与基因组百科全书(KEGG)和Meta Cye数据库预测其代谢通路和功能基因,采用线性判别分析和广义线性回归,筛选差异菌群以及探究其与相关表型的联系。结果中高ASCVD10年发病风险人群的α多样性显著降低(t=-8.213,P=0.032)。与产丁酸盐密切相关的菌种如单形拟杆菌(Bacteroides uniformis,LDA=4.035,P=0.001)、普拉梭菌(Faecalibacterium prausnitzii,LDA=3.876,P=0.003)、卵形拟杆菌(Bacteroides ovatus,LDA=3.648,P=0.006)、脆弱拟杆菌(Bacteroides fragilis,LDA=3.604,P=0.003)、双环瘤胃球菌(Ruminococcus bicirculans,LDA=3.188,P=0.009)、人罗斯拜瑞菌(Roseburia hominis,LDA=3.169,P=0.004)在低ASCVD10年风险人群中富集。并且涉及脂多糖合成(LDA=2.619,P=0.004)和脂质代谢(LDA=2.694,P=0.001)相关的通路和功能基因均在中高ASCVD 10年风险人群显著上调。结论中高ASCVD10年发病风险人群的肠道微生物和代谢功能明显改变,肠道菌群失调可能也是改变人群ASCVD 10年发病风险的重要原因之一。Objective To explore the differences of intestinal flora,metabolic pathways,and functional genes among people at ten-year risk of atherosclerotic cardiovascular disease(ASCVD)in Tibetan population.Methods Based on the follow-up survey data of the natural population cohort in Lhasa in southwest China,a total of 94 people were included in the“China Blood Lipid Management Guide 2023”for follow-up analysis.DNA was extracted from stool samples and analyzed by macro genomic sequencing.The composition of intestinal flora of people at different 10-year risks of ASCVD was compared by bioinformatics method.The metabolic pathway and functional genes were predicted by Kyoto Encyclopedia of Gene and Genome(KEGG)and MetaCye database.Linear discriminant analysis and generalized linear regression were used to screen differential bacteria and explore their relationship with related phenotypes.Results Theαdiversity of people at risk of ASCVD in the middle and high 10-year risk was significantly decreased(t=-8.213,P=0.032).Strains closely related to butyrate production such as Bacteroides uniforms,(LDA=4.035,P=0.001),Faecalibacterium prausnitzii(LDA=3.876,P=0.003),Bacteroides ovatus(LDA=3.648,P=0.006),Bacteroides fragilis(LDA=3.604,P=0.003),Ruminococcus bicirculans(LDA=3.188,P=0.009),and Roseburia hominis(LDA=3.169,P=0.004)were enriched in the population with low 10-year risk of ASCVD.The pathways and functional genes related to lipopolysaccharide synthesis(LDA=2.619,P=0.004)and lipid metabolism(LDA=2.694,P=0.001)were significantly up-regulated in the middle and high 10-year ASCVD risk population.Conclusion The intestinal microflora and metabolic function of the people at 10-year risk of ASCVD are significantly changed,and the imbalance of intestinal flora may also be one of the important reasons for changing the 10-year risk of ASCVD.

关 键 词：ASCVD10年发病风险 肠道菌群 宏基因组学 

分 类 号：R543.5[医药卫生—心血管疾病]