Li Yihui, Fu Ru, Li Ruixuan, Zeng Jianwei, Liu Tao, Li Xiaogang, Jiang Weihong
Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China.
Front Cardiovasc Med. 2023 May 4;10:1167346. doi: 10.3389/fcvm.2023.1167346. eCollection 2023.
BACKGROUND & AIMS: The pathogenesis of hypertension involves a diverse range of genetic, environmental, hemodynamic, and more causative factors. Recent evidence points to an association between the gut microbiome and hypertension. Given that the microbiota is in part determined by host genetics, we used the two-sample Mendelian randomization (MR) analysis to address the bidirectional causal link between gut microbiota and hypertension.
We selected genetic variants ( < 1 × 10) for gut microbiota ( = 18,340) from the MiBioGen study. Genetic association estimates for hypertension were extracted from genome-wide association study (GWAS) summary statistics on 54,358 cases and 408,652 controls. Seven complementary MR methods were implemented, including the inverse-variance weighted (IVW) method, followed by sensitivity analyses to verify the robustness of the results. Reverse-direction MR analyses were further conducted to probe if there was a reverse causative relationship. Bidirectional MR analysis then examines a modulation of gut microbiota composition by hypertension.
At the genus level, our MR estimates from gut microbiome to hypertension showed that there were 5 protective factors , , , and (id.1000000073), while 6 genera , , , , , and (id.2041) are risk factors. The and were detrimental and beneficial at the family level, respectively. In contrast, the MR results of hypertension-gut flora showed hypertensive states can lead to an increased abundance of E, , and and a lower abundance of , , , and .
Altered gut microbiota is a causal factor in the development of hypertension, and hypertension causes imbalances in the intestinal flora. Substantial research is still needed to find the key gut flora and explore the specific mechanisms of their effects so that new biomarkers can be found for blood pressure control.
高血压的发病机制涉及多种遗传、环境、血流动力学及其他致病因素。近期证据表明肠道微生物群与高血压之间存在关联。鉴于微生物群部分由宿主基因决定，我们采用两样本孟德尔随机化（MR）分析来探讨肠道微生物群与高血压之间的双向因果关系。
我们从MiBioGen研究中选择了肠道微生物群的遗传变异（<1×10）（n = 18340）。高血压的遗传关联估计值从对54358例病例和408652例对照的全基因组关联研究（GWAS）汇总统计数据中提取。实施了七种互补的MR方法，包括逆方差加权（IVW）方法，随后进行敏感性分析以验证结果的稳健性。进一步进行反向MR分析以探究是否存在反向因果关系。双向MR分析则研究高血压对肠道微生物群组成的调节作用。
在属水平上，我们从肠道微生物群到高血压的MR估计表明，有5个保护因素，即[具体名称1]、[具体名称2]、[具体名称3]、[具体名称4]和[具体名称5]（id.1000000073），而6个属，即[具体名称6]、[具体名称7]、[具体名称8]、[具体名称9]、[具体名称10]和[具体名称11]（id.2041）是危险因素。[具体名称12]和[具体名称13]在家族水平上分别是有害和有益的。相比之下，高血压-肠道菌群的MR结果显示高血压状态可导致[具体名称14]、[具体名称15]和[具体名称16]丰度增加，而[具体名称17]、[具体名称18]、[具体名称19]和[具体名称20]丰度降低。
肠道微生物群改变是高血压发生发展的一个因果因素，且高血压会导致肠道菌群失衡。仍需大量研究来寻找关键肠道菌群并探索其作用的具体机制，以便找到用于血压控制的新生物标志物。
