Abstract
The oral microbiome has the potential to provide an important symbiotic function in human blood pressure physiology by contributing to the generation of nitric oxide (NO), an essential cardiovascular signaling molecule. NO is produced by the human body via conversion of arginine to NO by endogenous nitric oxide synthase (eNOS) but eNOS activity varies by subject. Oral microbial communities are proposed to supplement host NO production by reducing dietary nitrate to nitrite via bacterial nitrate reductases. Unreduced dietary nitrate is delivered to the oral cavity in saliva, a physiological process termed the enterosalivary circulation of nitrate. Previous studies demonstrated that disruption of enterosalivary circulation via use of oral antiseptics resulted in increases in systolic blood pressure. These previous studies did not include detailed information on the oral health of enrolled subjects. Using 16S rRNA gene sequencing and analysis, we determined whether introduction of chlorhexidine antiseptic mouthwash for 1 week was associated with changes in tongue bacterial communities and resting systolic blood pressure in healthy normotensive individuals with documented oral hygiene behaviors and free of oral disease. Tongue cleaning frequency was a predictor of chlorhexidine-induced changes in systolic blood pressure and tongue microbiome composition. Twice-daily chlorhexidine usage was associated with a significant increase in systolic blood pressure after 1 week of use and recovery from use resulted in an enrichment in nitrate-reducing bacteria on the tongue. Individuals with relatively high levels of bacterial nitrite reductases had lower resting systolic blood pressure. These results further support the concept of a symbiotic oral microbiome contributing to human health via the enterosalivary nitrate-nitrite-NO pathway. These data suggest that management of the tongue microbiome by regular cleaning together with adequate dietary intake of nitrate provide an opportunity for the improvement of resting systolic blood pressure.
Highlights
The human oral cavity is an important habitat for microbes, and a healthy mouth can harbor upwards of ten billion bacteria (Loesche, 1993)
Tongue microbiome communities are of general interest in Eastern medicine because the appearance of the tongue coating is considered a manifestation of systemic health (Jiang et al, 2012a)
Regular tongue cleaning is recommended by the American Dental Association based on evidence that cleaning can reduce the severity of halitosis (Pedrazzi et al, 2016), there are no epidemiological data on tongue cleaning practices or frequency in the United States population
Summary
The human oral cavity is an important habitat for microbes, and a healthy mouth can harbor upwards of ten billion bacteria (Loesche, 1993). The enterosalivary nitrate-nitrite-NO pathway in humans appears to serve as an alternative pathway for production of bioactive NO, supplementing host endothelial NO production This pathway functions via the bacterial conversion of dietary nitrate into nitrites that can be converted to NO and participate in the regulation of endothelial vasodilation (Figure 1B) (Benjamin et al, 1994; Lundberg et al, 1994). This diet-dependent pathway relies upon commensal oral bacteria located on the tongue dorsum to perform the first step (nitrate reduction to nitrite) since mammals lack a functional nitrate reductase (Lundberg et al, 2004; Doel et al, 2005)
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