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

Graphical abstract

Highlights

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  This study has provided comprehensive evidence to support strong associations between oral microbiota and HTN. We discovered that 14 salivary genera and 15 subgingival genera were significantly altered in hypertension participants.

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  Fifteen oral genera were first found to associate with blood pressure. There were also new associations between oral microbiota and other clinical parameters been established.

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  This study has identified the shared genera that coexisted in saliva, subgingival plaques, and feces and illustrated the associations of the shared genera between oral and gut sample types.

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  This study has identified important oral-gut transmitting microbes in hypertension. Sixteen species under 5 genera were identified as oral-gut transmitters. Particularly, Veillonella was identified as a frequent oral-gut transmitter stably enriched in hypertension participants.

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  This study has demonstrated the potential causal link between oral-gut microbial transmission and hypertension—saliva from participants with hypertension exacerbated angiotensin II-induced hypertension in animal study. Veillonella could colonize in the gut of all mice receiving human saliva and more enriched in mice receiving saliva from hypertension participants.

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.