Roles of oral microbiota and oral-gut microbial transmission in hypertension

Bo-Yan Chen; Wen-Zhen Lin; Yu-Lin Li; Chao Bi; Lin-Juan Du; Yuan Liu; Lu-Jun Zhou; Ting Liu; Shuo Xu; Chao-Ji Shi; Hong Zhu; Yong-Li Wang; Jian-Yong Sun; Yan Liu; Wu-Chang Zhang; Hai-Xia Lu; Yi-Hua Wang; Qiang Feng; Fu-Xiang Chen; Chang-Qian Wang; Maurizio S Tonetti; Ya-Qin Zhu; Huili Zhang; Sheng-Zhong Duan

doi:10.1016/j.jare.2022.03.007

Roles of oral microbiota and oral-gut microbial transmission in hypertension

J Adv Res. 2023 Jan:43:147-161. doi: 10.1016/j.jare.2022.03.007. Epub 2022 Mar 19.

Authors

Bo-Yan Chen¹, Wen-Zhen Lin², Yu-Lin Li¹, Chao Bi³, Lin-Juan Du¹, Yuan Liu¹, Lu-Jun Zhou², Ting Liu¹, Shuo Xu¹, Chao-Ji Shi⁴, Hong Zhu¹, Yong-Li Wang¹, Jian-Yong Sun¹, Yan Liu¹, Wu-Chang Zhang¹, Hai-Xia Lu⁵, Yi-Hua Wang⁶, Qiang Feng⁶, Fu-Xiang Chen⁷, Chang-Qian Wang⁸, Maurizio S Tonetti⁹, Ya-Qin Zhu¹⁰, Huili Zhang¹¹, Sheng-Zhong Duan¹²

Affiliations

¹ Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China.
² Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China; Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Stomatology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
⁴ National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China; Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China; Department of Preventive Dentistry, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Department of Human Microbiome, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.
⁷ Department of Clinical Immunology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁸ Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁹ National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China; Department of Oral and Maxillofacial Implantology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁰ National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China; Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: zyq1590@163.com.
¹¹ Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: huilizhang815@163.com.
¹² Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China. Electronic address: duansz@shsmu.edu.cn.

Abstract

Introduction: Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered.

Objectives: To characterize the alterations of oral and gut microbiota and their roles in HTN.

Methods: We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN.

Results: BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition.

Conclusions: PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.

Keywords: Blood pressure; Gut microbiota; Hypertension; Oral microbiota; Oral-gut axis; Veillonella.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cross-Sectional Studies
Follow-Up Studies
Gastrointestinal Microbiome* / physiology
Humans
Hypertension*
Mice
Mice, Inbred C57BL
Microbiota*
Periodontitis*
RNA, Ribosomal, 16S / genetics

Substances

RNA, Ribosomal, 16S