Background: Recently, the potential role of gut microbiome in metabolic diseases has been revealed, especially in cardiovascular diseases. Hypertension is one of the most prevalent cardiovascular diseases worldwide, yet whether gut microbiota dysbiosis participates in the development of hypertension remains largely unknown. To investigate this issue, we carried out comprehensive metagenomic and metabolomic analyses in a cohort of 41 healthy controls, 56 subjects with pre-hypertension, 99 individuals with primary hypertension, and performed fecal microbiota transplantation from patients to germ-free mice. Results: Compared to the healthy controls, we found dramatically decreased microbial richness and diversity, Prevotelladominated gut enterotype, distinct metagenomic composition with reduced bacteria associated with healthy status and overgrowth of bacteria such as Prevotella and Klebsiella, and disease-linked microbial function in both pre-hypertensive and hypertensive populations. Unexpectedly, the microbiome characteristic in pre-hypertension group was quite similar to that in hypertension. The metabolism changes of host with pre-hypertension or hypertension were identified to be closely linked to gut microbiome dysbiosis. And a disease classifier based on microbiota and metabolites was constructed to discriminate pre-hypertensive and hypertensive individuals from controls accurately. Furthermore, by fecal transplantation from hypertensive human donors to germ-free mice, elevated blood pressure was observed to be transferrable through microbiota, and the direct influence of gut microbiota on blood pressure of the host was demonstrated. Conclusions: Overall, our results describe a novel causal role of aberrant gut microbiota in contributing to the pathogenesis of hypertension. And the significance of early intervention for pre-hypertension was emphasized.
基金:
National Basic Research Program of China (973 Program)National Basic Research Program of China [2014CB542302, 2015CB554200]; CAMS Innovation Fund for Medical Science (CIFMS) [2016-I2M-1-006]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81470541, 81630014, 91531306, 81500383]; Beijing Municipal Science and Technology CommissionBeijing Municipal Science & Technology Commission [Z151100002115050, Z151100004015176]; Beijing Municipal Commission of EducationBeijing Municipal Commission of Education [KZ201610025028]; International S&T Cooperation Program of China [2013DFB30310]; AHA Scientist Development GrantAmerican Heart Association [12SDG11680011]
第一作者单位:[1]Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis China, Hypertens Ctr,State Key Lab Cardiovasc Dis China, Beijing 100037, Peoples R China[2]Peking Union Med Coll, Beijing 100037, Peoples R China[3]Capital Med Univ, Beijing ChaoYang Hosp, Dept Cardiol, Beijing 100020, Peoples R China[4]Beijing Key Lab Hypertens, Beijing 100020, Peoples R China
通讯作者:
通讯机构:[1]Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis China, Hypertens Ctr,State Key Lab Cardiovasc Dis China, Beijing 100037, Peoples R China[2]Peking Union Med Coll, Beijing 100037, Peoples R China[3]Capital Med Univ, Beijing ChaoYang Hosp, Dept Cardiol, Beijing 100020, Peoples R China[4]Beijing Key Lab Hypertens, Beijing 100020, Peoples R China[15]Chinese Acad Sci, Inst Microbiol, Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China[16]Zhejiang Univ, Affiliated Hosp 1, Coll Med, Collaborat Innovat Ctr Diag & Treatment Infect D, Hangzhou 310003, Zhejiang, Peoples R China
推荐引用方式(GB/T 7714):
Li Jing,Zhao Fangqing,Wang Yidan,et al.Gut microbiota dysbiosis contributes to the development of hypertension[J].MICROBIOME.2017,5:14.doi:10.1186/s40168-016-0222-x.
APA:
Li, Jing,Zhao, Fangqing,Wang, Yidan,Chen, Junru,Tao, Jie...&Cai, Jun.(2017).Gut microbiota dysbiosis contributes to the development of hypertension.MICROBIOME,5,
MLA:
Li, Jing,et al."Gut microbiota dysbiosis contributes to the development of hypertension".MICROBIOME 5.(2017):14