基于孟德尔随机化探索肠道微生物和血液代谢物与高血压及其并发症之间的因果关系

Exploring the Causal Relationship Between Gut Microbiota and Blood Metabolites on Hypertension and Hypertension-Related Complications Based on Mendelian Randomization

目的使用孟德尔随机化方法探究肠道微生物和血液代谢物与高血压及其并发症之间的因果关系。方法从MiBioGen联盟和大型全基因组关联分析中获取肠道微生物和血液代谢物的汇总数据,并获取与其显著相关的遗传变异作为工具变量。高血压、高血压心脏病、高血压肾病和卒中的汇总数据来自于芬兰基因组研究和其他大型全基因组关联分析。使用两样本孟德尔随机化分析探究肠道微生物和血液代谢物与高血压、高血压心脏病和高血压肾病之间的潜在关联,使用中介孟德尔随机化探究体重指数在其中的潜在效应。结果研究结果表明,当使用P<5×10^(-8)筛选暴露的工具变量时,共有4种肠道微生物与高血压具有因果关系,3种与高血压心脏病相关。共有13种血液代谢物与高血压及其并发症具有因果关系,其中family Streptococcaceae(OR=2.447,P=0.046)和genus Streptococcus(OR=2.338,P=0.046)可能是高血压和高血压心脏病的共同危险因素。当阈值设置为P<5×10^(-5)时,经过P值校正,分别有8种肠道微生物和10种血液代谢物与高血压及其并发症存在因果关系,其中family Bacteroidaceae(OR=0.935,P=0.005)对高血压具有保护作用,class Betaproteobacteria(OR=0.940,P=0.008)可能会导致卒中发生风险的降低。结论遗传预测的多种特定肠道微生物和血液代谢物与高血压及其并发症之间具有因果关系,这些菌群和血液代谢物可能成为新的生物标志物,为高血压及其并发症的预防、早期筛查和治疗提供新的思路,未来需更多的基础和临床研究进行验证。

Objective To explore the causal relationship between gut microbiota and blood metabolites and hypertension and its complications using Mendelian randomization method.Methods Collect summary statistical data on gut microbiota and blood metabolites from the MiBioGen consortium and large-scale genome-wide association studies,and obtain genetic variations significantly associated with them as instrumental variables.The summary statistical data for hypertension,hypertensive heart disease,hypertensive kidney disease,and stroke were obtained from the Finnish Genome Research Project and other large-scale genome-wide association studies.Two sample Mendelian randomization analysis was used to explore the potential association between gut microbiota and blood metabolites with hypertension,hypertensive heart disease,and hypertensive kidney disease,and mediation Mendelian randomization was used to investigated the potential effects of body mass index.Results The research results indicate that when using P<5×10^(-8) to screen for exposed instrumental variables,a total of 4 gut microbiota have a causal relationship with hypertension,and 3 are associated with hypertensive heart disease.There are a total of 13 blood metabolites that have a causal relationship with hypertension and its complications,among which family Streptococcaceae(OR=2.447,P=0.046)and genus Streptococcus(OR=2.338,P=0.046)may be common risk factors for hypertension and hypertensive heart disease.When the threshold is set to P<5×10^(-5),after P-value correction,there are causal relationships between 8 gut microbiota and 10 blood metabolites and hypertension and its complications,respectively.Among them,family Bacteroidaceae(OR=0.935,P=0.005)has a protective effect on hypertension,while class Betaproteobacteria(OR=0.940,P=0.008)may lead to a reduced risk of stroke.Conclusion There is a causal relationship between various specific gut microbiota and blood metabolites predicted by genetics and hypertension and its complications.These microbiota and blood metabolites may become new biomarkers,providing new ideas for the prevention,early screening,and treatment of hypertension and its complications.More basic and clinical research is needed to verify this in the future.