Frequency of Tongue Cleaning Impacts the Human Tongue Microbiome Composition and Enterosalivary Circulation of Nitrate

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.

Topic Application of the Probiotic Streptococcus dentisani Improves Clinical and Microbiological Parameters Associated With Oral Health

“…Unexpectedly, the number of toothbrushings per day reported by participants at baseline correlated with S. dentisani levels at V0 ( Supplementary Table 2 ). This, together with the increase in S. dentisani not only in the probiotic group but also in the placebo ( Supplementary Figure 6 ), suggests that this species is favored by plaque removal, as it has been shown for other aerobic or facultatively anaerobic species in tongue biofilms (Tribble et al, 2019 ).…”

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

“…Evaluation of home BP in this study revealed that the BP effect was apparent within 1 day of mouthwash use, with no evidence of tachyphylaxis over the week-long period of intervention (Kapil et al, 2013). This effect of increasing Nitrate-Nitrite-Nitric Oxide Pathway BP with disruption of the enterosalivary circulation has been confirmed in further studies, including in healthy volunteers (n 5 27) with confirmed disease-free oral health status at baseline using chlorhexidine twice daily for 7 days (Tribble et al, 2019). Importantly, this effect is also seen in patients with CVD.…”

How Periodontal Disease and Presence of Nitric Oxide Reducing Oral Bacteria Can Affect Blood Pressure

“…[ 75 ]. It was noticed that there was an inter-subject variability in response to 7 days of treatment with chlorhexidine dependent upon the composition of the baseline tongue microbiota with a significant change in SBP between the treatment and 3-days recovery time points (115 vs. 111.5 mmHg) [ 76 ]. Tongue bacterial community composition was influenced by daily cleaning (either once or twice) [ 43 ].…”

“…Rapid nitrate/nitrite reducing bacteria recovery is observed in patients with frequent tongue cleaning as well as an increase in the nitrate reduction metabolic activity. This may also activate bacterial metabolism [ 76 ]. Studies on animal models suggest that the use of chlorhexidine mouthwash prevents nitrite formation in the oral cavity, consequently nitrite does not enter the acidic environment of the stomach thus weakening the s-nitrosylation process [ 28 ].…”