首页|肠道菌群与脑卒中的因果关联:一项两样本孟德尔随机化分析

肠道菌群与脑卒中的因果关联:一项两样本孟德尔随机化分析

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目的 利用孟德尔随机化(Mendelian randomization,MR)方法探究肠道菌群与脑卒中的因果关联.方法 采用公共数据库MiBioGen研究的肠道菌群全基因组关联分析研究(genome wide association study,GWAS)数据(n=13 266)和IEU Open GWAS数据库的脑卒中GWAS数据,根据预设的阈值提取与肠道菌群属水平相对丰度显著相关的独立遗传位点作为工具变量(instrumental variables,IVs).主要采用逆方差加权法进行分析,根据效应指标优势比(odds ratio,OR)和95%置信区间(confidence interval,CI)评估结果.使用留一法、异质性检验、水平基因多效性检验验证结果的稳定性和可靠性.结果 LachnospiraceaeFCS020group 属、LachnospiraceaeNK4A136group 属、RuminococcaceaeUCG004属和Intestinimonas属丰度的升高可降低脑卒中的患病风险,OR(95%CI)分别为0.914(0.845~0.988)、0.909(0.838~0.985)、0.919(0.849~0.995)、0.924(0.866~0.987).Allisonella 属、Gordonibacter 属、Paraprevotella 属和 Streptococcus 属丰度的升高可增加脑卒中的患病风险,OR(95%CI)分别为 1.103(1.039~1.171)、1.056(1.009~1.105)、1.078(1.013~1.147)、1.110(1.020~1.209).留一法分析显示结果稳定,不存在对结果有强影响的IVs,且可剔除异质性和水平基因多效性对因果效应估计产生的影响.结论 LachnospiraceaeFCS020group 属、LachnospiraceaeNK4A136group 属、RuminococcaceaeUCG004属和Intestinimonas属有益于预防脑卒中的因素可降低发病风险;而Allisonella属、Gordonibacter属、Paraprevotella属和Streptococcus属作用因素相反,与脑卒中发生呈正相关.益生菌治疗脑卒中可能成为未来临床或机制方面研究的趋势.
Causal association between gut microbiota and stroke:A two-sample Mendelian randomization analysis
Objective To investigate causal relationship between gut microbiota and stroke by using Mendelian randomization(MR).Methods The gut microbiota genome wide association study(GWAS)data of MiBioGen study in public database(n=13 266)and stroke GWAS data of IEU Open GWAS were used.Independent genetic loci significantly correlated with the relative abundance of gut microbiota at genus level were used for instrumental variables(Ⅳs)according to preset thresholds.The inverse variance weighted method was used to analyse,results were evaluted according to odds ratio(OR)of effect index and 95%confidence interval(CI).The stability and reliability of the results were verified by leave one out,heterogeneity test and horizontal gene pleiotropy test.Results The rise of abundance of LachnospiraceaeFCS020group genera,Lachnospiraceae NK4A136group genera,RuminococcaceaeUCG004 genera and Intestinimonas genera,could reduce the risk of stroke,the OR(95%CI)were 0.914(0.845-0.988),0.909(0.838-0.985),0.919(0.849-0.995),0.924(0.866-0.987),respectively.The increase of abundance of Allisonella genera,Gordonibacter genera,Paraprevotella genera and Streptococcus genera can increase the risk of stroke,and the OR(95%CI)were 1.103(1.039-1.171),1.056(1.009-1.105),1.078(1.013-1.147),1.110(1.020-1.209),respectively.Leave one out showed that the results were stable,there were no IVs that had a strong influence on the results,and the influence of heterogeneity and horizontal gene pleiotropy on the estimation of causal effect could be eliminated.Conclusion The levels of Lachnospiraceae FCS020group genera,LachnospiraceaeNK4A136group genera,RuminococcaceaeUCG004 genera and Intestinimonas genera protect factors of brain stroke,with the increase of bacterial abundance,the incidence of stroke may be reduced.On the contrary,the levels of Allisonella genera,Gordonibacter genera,Paraprevotella genera and Streptococcus genera are positively correlated with stroke occurrence.Probiotics in the treatment of stroke may become the trend of future clinical or mechanism research.

Gut microbiotaStrokeMendelian randomization

尹平平、王磊

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湖南省人民医院(湖南师范大学附属第一医院)康复医学科,湖南长沙 410000

肠道菌群 脑卒中 孟德尔随机化

2024

中国现代医生
中国医学科学院

中国现代医生

影响因子:1.571
ISSN:1673-9701
年,卷(期):2024.62(24)