title: Gut microbiota dysbiosis contributes to the development of hypertension.
abstract: 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.
  
  
  
  Compared to the healthy controls, we found dramatically decreased microbial richness and diversity, Prevotella-dominated 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.
  
  
  
  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.
authors.affiliation: Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.|Department of Cardiology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, China.|Beijing Key Laboratory of Hypertension, Beijing, 100020, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Computational Genomics Laboratory, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Fangqing
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Novogene Bioinformatics Institute, Beijing, 100000, China.
authors.forename: Junru
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Baoding NO.1 Central Hospital, Baoding, 071000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Tian
authors.affiliation: Department of Cardiology Kailuan General Hospital, Hebei Union University, Tangshan, 063000, China.
authors.forename: Shouling
authors.initials: S
authors.lastname: Wu
authors.affiliation: Novogene Bioinformatics Institute, Beijing, 100000, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Biomedical Informatics, Centre for Noncoding RNA Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
authors.affiliation: Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, 77204, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Weldon
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, 77204, USA.
authors.forename: Kelda
authors.initials: K
authors.lastname: Auguste
authors.affiliation: Medical Research Center, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Medical Research Center, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, 77204, USA.|Department of Stem Cell Engineering, Texas Heart Institute, Houston, TX, 77030, USA.|Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, China. yxc6229@sina.com.|Beijing Key Laboratory of Hypertension, Beijing, 100020, China. yxc6229@sina.com.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. zhubaoli@im.ac.cn.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China. zhubaoli@im.ac.cn.
authors.forename: Baoli
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Hypertension Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China. caijun@fuwaihospital.org.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D015331:Cohort Studies; D064806:Dysbiosis; D000075222:Essential Hypertension; D000069467:Fecal Microbiota Transplantation; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005856:Germ-Free Life; D006801:Humans; D006973:Hypertension / Q000382:microbiology*; D007709:Klebsiella / Q000235:genetics / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058246:Prehypertension / Q000382:microbiology*; D018720:Prevotella / Q000235:genetics / Q000302:isolation & purification; D011446:Prospective Studies
keywords: Fecal transplant; Gut microbiota; Hypertension; Metabolism; Pre-hypertension