Zhang Yuxuan, Zhang Xinyi, Chen Delong, Lu Jia, Gong Qinyan, Fang Jiacheng, Jiang Jun
Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Department of Cardiology, The First People's Hospital of Jiashan, Jiaxing, China.
Front Cardiovasc Med. 2022 Aug 30;9:971376. doi: 10.3389/fcvm.2022.971376. eCollection 2022.
Observational studies have shown gut microbiomes were associated with cardiovascular diseases (CVDs), but their roles remain controversial, and these associations have not yet been established causally.
Two-sample Mendelian randomization (MR) was used to investigate whether gut microbiome had a causal effect on the risk of CVDs. To obtain comprehensive results, we performed two sets of MR analyses, one with single nucleotide polymorphisms (SNPs) that smaller than the genome-wide statistical significance threshold (5 × 10) as instrumental variables, and the other with SNPs that lower than the locus-wide significance level (1 × 10). Summary-level statistics for CVDs, including coronary artery disease (CAD), myocardial infarction, heart failure, atrial fibrillation, stroke and its subtypes were collected. The ME estimation was performed using the inverse-variance weighted and Wald ratio methods. Sensitivity analysis was performed using the weighted median, MR-Egger, leave-one-out analysis, MR pleiotropy residual sum and outlier and MR Steiger.
Based on the locus-wide significance level, genetically predicted genus was positively associated with the risk of CAD (odds ratio (OR) = 1.06, 95% confidence interval (CI), 1.03 - 1.10, = 1.67 × 10), family was negatively correlated with stroke risk (OR = 0.83,95% CI, 0.75-0.93, = 7.76 × 10) and ischemic stroke risk (OR = 0.823,95% CI, 0.74-0.92, = 4.15 × 10). There was no causal relationship between other genetically predicted gut microbiome components and CVDs risk. Based on the genome-wide statistical significance threshold, the results showed that the gut microbiome had no causal relationship with CVDs risk.
Our findings reveal that there are beneficial or adverse causal effects of gut microbiome components on CVDs risk and provide novel insights into strategies for the prevention and management of CVDs through the gut microbiome.
观察性研究表明肠道微生物群与心血管疾病（CVD）有关，但其作用仍存在争议，且这些关联尚未建立因果关系。
采用两样本孟德尔随机化（MR）方法研究肠道微生物群是否对心血管疾病风险有因果影响。为了获得全面的结果，我们进行了两组MR分析，一组使用小于全基因组统计显著性阈值（5×10）的单核苷酸多态性（SNP）作为工具变量，另一组使用低于基因座显著性水平（1×10）的SNP。收集了心血管疾病的汇总统计数据，包括冠状动脉疾病（CAD）、心肌梗死、心力衰竭、心房颤动、中风及其亚型。使用逆方差加权法和Wald比率法进行效应估计。使用加权中位数、MR-Egger、留一法分析、MR多效性残差总和与异常值以及MR Steiger进行敏感性分析。
基于基因座显著性水平，基因预测的属与CAD风险呈正相关（优势比（OR）=1.06，95%置信区间（CI），1.03 - 1.10，P = 1.67×10），科与中风风险呈负相关（OR = 0.83，95%CI，0.75 - 0.93，P = 7.76×10）和缺血性中风风险呈负相关（OR = 0.823，95%CI，0.74 - 0.92，P = 4.15×10）。其他基因预测的肠道微生物群成分与心血管疾病风险之间没有因果关系。基于全基因组统计显著性阈值，结果表明肠道微生物群与心血管疾病风险没有因果关系。
我们的研究结果揭示了肠道微生物群成分对心血管疾病风险有有益或有害的因果影响，并为通过肠道微生物群预防和管理心血管疾病的策略提供了新的见解。
