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.
Failure to produce sufficient NO is causal for the onset and progression of a number of cardiovascular diseases, including hypertension and atherosclerosis ( Taddei et al., 2001 Torregrossa et al., 2011). However, the eNOS gene is polymorphic, and the pathway can become dysfunctional with age ( Niu and Qi, 2011). The human body is able to produce NO directly by the five-electron oxidation of L-arginine ( Moncada and Higgs, 1993) by endothelial nitric oxide synthases (eNOS Figure 1A). Continuous generation of NO is essential for the integrity of the cardiovascular system, and decreased production or bioavailability of NO is central to the development of many heart-related disorders ( Lundberg et al., 2004, 2009 Bryan and Loscalzo, 2017). Cardiovascular research has identified a potential role for the oral microbiome in human health via the conversion of dietary nitrate into nitrite, the bioactive storage pool available for spontaneous conversion to nitric oxide (NO) ( Lundberg and Govoni, 2004 Lundberg et al., 2008).
The human oral cavity is an important habitat for microbes, and a healthy mouth can harbor upwards of ten billion bacteria ( Loesche, 1993). 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. These results further support the concept of a symbiotic oral microbiome contributing to human health via the enterosalivary nitrate-nitrite-NO pathway. Individuals with relatively high levels of bacterial nitrite reductases had lower resting systolic blood pressure. 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. Tongue cleaning frequency was a predictor of chlorhexidine-induced changes in systolic blood pressure and tongue microbiome composition.
Measure frequency of values in statplus free#
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. These previous studies did not include detailed information on the oral health of enrolled subjects. Previous studies demonstrated that disruption of enterosalivary circulation via use of oral antiseptics resulted in increases in systolic blood pressure. Unreduced dietary nitrate is delivered to the oral cavity in saliva, a physiological process termed the enterosalivary circulation of nitrate. Oral microbial communities are proposed to supplement host NO production by reducing dietary nitrate to nitrite via bacterial nitrate reductases. 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. 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. 6Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.5Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States.4Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX, United States.3SynBioBeta, Pleasant Hill, CA, United States.2Division of Cardiology, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center Houston, Houston, TX, United States.1Department of Periodontics, School of Dentistry, The University of Texas Health Science Center Houston, Houston, TX, United States.Gay 1 †, Kavitha Parthasarathy 1, Doan-Hieu V. Tribble 1 *, Nikola Angelov 1, Robin Weltman 1, Bing-Yan Wang 1, Sridhar V.
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