Zhu Sibo, Xu Kelin, Jiang Yanfeng, Zhu Chengkai, Suo Chen, Cui Mei, Wang Yingzhe, Yuan Ziyu, Xue Jiangli, Wang Jiucun, Zhang Tiejun, Zhao Genming, Ye Weimin, Huang Tingting, Lu Ming, Tian Weizhong, Jin Li, Chen Xingdong
State Key Laboratory of Genetic Engineering and Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China.
Fudan University Taizhou Institute of Health Sciences, Taizhou, China.
Rheumatology (Oxford). 2021 Dec 24;61(1):258-269. doi: 10.1093/rheumatology/keab309.
An altered microbiota, which can be described quantitatively, has been identified as playing a pivotal role in host vascular physiology, and it may contribute to various diseases. The aim of this study was to better understand the role of the gut microbiota in vascular physiology in a subclinical elderly population, and to investigate how lifestyle affects the composition of host gut microbiota to further impact the pathogenesis of vascular diseases.
We performed a population-based faecal metagenomic study over 569 elderly asymptomatic subclinical individuals in rural China. An association network was built based on clinical measurements and detailed epidemiologic questionnaires, including blood chemistry, arterial stiffness, carotid ultrasonography, and metagenomic datasets.
By analyzing the breadth, depth and impact of each node of the association network, we found carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were essential in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of eating fresh fruits and vegetables, and more exercise significantly reduced carotid atherosclerosis in terms of IMT, peak systolic velocity and end-diastolic velocity values through the mediation of Alistepes, Oligella and Prevotella. Gut microbes explained 16.5% of the mediation effect of lifestyle on the pathogenesis of carotid atherosclerosis. After adjustment, Faecalicatena [odds ratio (OR) = 0.12 ∼0.65] was shown to be protective against the formation of carotid atherosclerosis, independently, while Libanicoccus (OR = 1.46 ∼4.20 ) was associated with increased carotid arterial IMT. KEGG/KO Kyoto Encyclopedia of Genes and Genomes/ KEGG Orthology (KEGG/KO) analyses revealed a loss of anti-inflammation function in IMT subjects.
Our study revealed a Chinese population-wide phenotype-metagenomic association network and a mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at potential therapeutic and preventive uses for microbiota in vascular diseases.
已确定可定量描述的微生物群改变在宿主血管生理中起关键作用，并可能导致各种疾病。本研究的目的是更好地了解肠道微生物群在亚临床老年人群血管生理中的作用，并研究生活方式如何影响宿主肠道微生物群的组成，进而影响血管疾病的发病机制。
我们对中国农村569名无症状亚临床老年人进行了基于人群的粪便宏基因组研究。基于临床测量和详细的流行病学调查问卷构建了一个关联网络，包括血液化学、动脉僵硬度、颈动脉超声检查和宏基因组数据集。
通过分析关联网络中每个节点的广度、深度和影响，我们发现颈动脉粥样硬化指标，包括内膜中层厚度（IMT），在网络中至关重要，并且与生活习惯、社会经济地位和饮食显著相关。使用中介分析，我们发现通过阿里斯泰普斯菌属、寡养单胞菌属和普雷沃菌属的中介作用，较高频率食用新鲜水果和蔬菜以及更多运动在IMT、收缩期峰值速度和舒张末期速度值方面显著降低颈动脉粥样硬化。肠道微生物解释了生活方式对颈动脉粥样硬化发病机制中介作用的16.5%。调整后，粪链菌属[比值比（OR）=0.12～0.65]被证明独立地对颈动脉粥样硬化的形成具有保护作用，而黎巴嫩球菌属（OR=1.46～4.20）与颈动脉内膜中层厚度增加有关。京都基因与基因组百科全书/京都基因与基因组百科全书直系同源基因（KEGG/KO）分析显示，IMT受试者的抗炎功能丧失。
我们的研究揭示了全中国人群的表型-宏基因组关联网络以及肠道微生物群对颈动脉粥样硬化的中介作用，提示微生物群在血管疾病中具有潜在的治疗和预防用途。
