Investigation of the Relationship Between Dietary Nitrate and Oral Microbiota in Children With Primary Hypertension

Primary hypertension (PH) in children and adolescents is increasingly recognized as a significant public health concern. Epidemiological data from multiple cohorts, including the Young Finns Study and other long-term follow-ups, demonstrate that elevated systolic blood pressure beginning in adolescence predicts endothelial dysfunction, increased carotid intima-media thickness, and a higher lifetime risk of cardiovascular morbidity. Children with PH frequently show early subclinical changes such as impaired flow-mediated dilation, increased arterial stiffness, heightened sympathetic activity, and altered nitric oxide (NO) bioavailability. Despite these findings, the early biological mechanisms that contribute to PH in youth remain insufficiently characterized, and non-invasive biomarkers for early detection are limited.

Recent advances in pediatric cardiovascular science suggest that the nitrate-nitrite-nitric oxide (NO₃- → NO₂- → NO) enterosalivary pathway may play a previously underappreciated role in blood pressure regulation. This pathway relies heavily on commensal oral bacteria capable of reducing dietary nitrate to nitrite, which is then swallowed and converted to NO systemically. Any disruption in this oral microbial nitrate-reducing capacity, whether due to dysbiosis, impaired oral hygiene, inflammation, dietary differences, or ecological shifts during adolescence may diminish NO bioavailability and subsequently raise blood pressure. Several adult studies have shown that antibacterial mouthwashes, changes in oral microbiota composition, and reduced salivary nitrate-reducing activity lead to measurable increases in systolic and diastolic blood pressure. However, pediatric data remain extremely scarce, with no comprehensive metagenomic investigation of oral microbiota in children with PH published to date.

This study is therefore designed to characterise, in detail, the relationships between (i) salivary microbiota composition, (ii) nitrate/nitrite conversion capacity, (iii) salivary biochemical characteristics, and (iv) blood pressure profiles in adolescents aged 12-18 years diagnosed with primary hypertension. Importantly, the project employs non-invasive sampling methods (stimulated and unstimulated saliva), enabling participation from children who may not tolerate venipuncture or invasive sampling procedures, and providing a practical model for future screening tools.

1. Scientific Rationale and Background 1.1. Pediatric Hypertension

Primary hypertension in youth was once considered rare but now affects up to 3-5% of adolescents globally. It is strongly associated with obesity, insulin resistance, sympathetic overactivation, endothelial dysfunction, and chronic inflammatory states. Although pharmacological treatment is increasingly used, current pediatric guidelines emphasise early identification and non-pharmacological management strategies.