高血压病是最常见的慢病，是中国乃至全球重要的公共卫生问题。近期有动物实验研究提示肠道微生物失调与高血压相关。本项目是申请人前一个国家自然基金课题的延续和深入，即在高血压、高血压前期及健康人肠道菌群宏基因组测序、高血压病人粪菌移植无菌小鼠诱发小鼠血压升高以及高血压病人血清代谢组学研究的基础上，进一步采集不同区域高血压病人标本扩大样本量进行肠道宏基因组分析，以明确高血压病人肠道菌群紊乱分子分型特征的普遍性；筛选代表性条件致病菌株进行无菌小鼠移植试验明确因果关系；并观察条件致病菌是否通过抗原介导的分子模式或损伤介导的分子模式活化机体免疫炎症反应；评估肠道菌群调节相关血清代谢小分子的血管损伤机制；观察干预肠道菌群对高血压防治的有效性，从而探讨肠道菌群微生态紊乱是高血压发病新的环境致病因素，明确肠道菌群导致血压调节障碍的病理生理机制。本项目的开展将对临床早期防治高血压提供新的靶点，具有重要的意义。

Essential hypertension is a most prevalent cardiovascular diseases, and becomes a serve global public health issue because of the high morbidity and potential risk to other cardiovascular diseases. Recently, several animal studies reported that the disorder of gut microbiome correlated with hypertension. Based on our previous work findings of metagenomics analysis, fecal transplantation and metabonomics changes in hypertension and pre-hypertension patients, we raised our hypothesis "Disorder of gut microbiome is a novel environmental pathogenic factor of essential hypertension". In this project, we plan to analyze the metagenomics in other two cohorts for conforming the universality of this pathogenic factor in human. Using isolated conditional pathogenic bacterium or its components to inoculatetransplant sterile germ-free mice, we aim to identify the key pathogenic bacterium for inducing hypertension. Next, we plan to observe the possible immunological injury by pathogen-associated molecular pattern pathway or damage-associated molecular pattern while giving pathogenic bacterium; or to observe vascular injury by the metabolic production to elucidate the pathophysiologcial mechanism of gut microbiome. Last, we plan to interference the disorder of gut microbiome to treat hypertensive rats, aim to evaluate the efficiency of therapy addressing gut microbiome as target. In the present project, we aim to give some evidences to support our hypothesis by these studies. By performing this project, we offer a novel common pathogenic factor of hypertension, and a novel preventive and therapeutic target of essential hypertension.