肠道微生物组与血压和血细胞计数的遗传关联及其作为中介物：两步孟德尔随机化分析。

Genetic association between gut microbiome and blood pressure and blood cell count as mediator: A two-step Mendelian randomization analysis.

机构信息

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.

出版信息

Gene. 2024 Oct 20;925:148573. doi: 10.1016/j.gene.2024.148573. Epub 2024 May 17.

DOI:10.1016/j.gene.2024.148573

PMID:38762013

Abstract

BACKGROUND

Previous studies have established a genetic link between gut microbiota and hypertension, but whether blood cell count plays a mediating role in this remains unknown. This study aims to explore genetic associations and causal factors involving the gut microbiome, peripheral blood cell count, and blood pressure.

METHODS

We utilized summary statistics derived from genome-wide association studies to conduct a two-sample mediation Mendelian randomization analysis (https://gwas.mrcieu.ac.uk/). We applied inverse variance weighted (IVW) estimation method as the primary method, along with MR Egger, Weighted median, Simple mode and Weighted mode as complementary methods. To ensure the robustness of the results, several sensitivity analyses were conducted.

RESULTS

Genetic variants significantly associated with the microbiome, blood pressure, or peripheral blood cell counts were selected as instrumental variables. Fourteen microbial taxa were found to have suggestive associations with diastolic blood pressure (DBP), while fifteen microbial taxa showed suggestive associations with systolic blood pressure (SBP). Meanwhile, red blood cell count, lymphocyte count, and platelet count were identified to mediate the influence of the gut microbiome on blood pressure. Specifically, red cell count was identified to mediate the effects of the phylum Cyanobacteria on DBP (mediated proportion: 8.262 %). Lymphocyte count was found mediate the effects of the genus Subdoligranulum (mediated proportion: 2.642 %) and genus Collinsella (mediated proportion: 2.749 %) on SBP. Additionally, platelet count was found to mediate the relationship between the genus Eubacterium ventriosum group and SBP, explaining 3.421 % of the mediated proportion.

CONCLUSIONS

Our findings highlighted that gut microbiota may have causal influence on the blood pressure by modulating blood cell counts, which sheds new light on the pathogenesis and potential clinical interventions through the intricate axis of gut microbiome, blood cell counts, and blood pressure.

摘要

背景

先前的研究已经证实了肠道微生物群与高血压之间存在遗传关联，但血细胞计数是否在其中发挥中介作用尚不清楚。本研究旨在探讨肠道微生物组、外周血细胞计数和血压之间的遗传关联和因果因素。

方法

我们利用来自全基因组关联研究的汇总统计数据进行了两样本中介孟德尔随机化分析（https://gwas.mrcieu.ac.uk/）。我们应用逆方差加权（IVW）估计方法作为主要方法，并结合 MR Egger、加权中位数、简单模式和加权模式作为补充方法。为了确保结果的稳健性，我们进行了几种敏感性分析。

结果

选择与微生物组、血压或外周血细胞计数显著相关的遗传变异作为工具变量。发现 14 个微生物类群与舒张压（DBP）具有提示性关联，而 15 个微生物类群与收缩压（SBP）具有提示性关联。同时，红细胞计数、淋巴细胞计数和血小板计数被确定为肠道微生物群对血压影响的中介因素。具体而言，红细胞计数被确定为蓝藻门对 DBP 的影响的中介因素（中介比例：8.262%）。淋巴细胞计数被发现介导了 Subdoligranulum 属（中介比例：2.642%）和 Collinsella 属（中介比例：2.749%）对 SBP 的影响。此外，血小板计数被发现介导了 Eubacterium ventriosum 组与 SBP 的关系，解释了 3.421%的中介比例。