Role of the Oral Microbiome in Blood Pressure Regulation in Pregnancy

Investigation of the Oral Microbiome in Pregnancy - do Differences in Oral Bacterial Profiles and Nitrate Metabolism Contribute to Blood Pressure Regulation in Pregnant Women?

High blood pressure in pregnancy is associated with poor outcomes for both mum and baby, increasing the risk of pregnancy complications including pre-eclampsia, fetal growth restriction and preterm birth. The development of new blood pressure lowering interventions suitable for use in pregnancy is a key research priority. Inorganic nitrate is a compound found in certain types of food, particularly green leafy vegetables and beetroot. Nitrate provides an important source of nitric oxide (NO), a molecule involved in keeping blood vessels healthy and regulating blood pressure. Supplementation with nitrate in the diet, using interventions such as beetroot juice, has been shown to reduce blood pressure and improve blood vessel function. In order for dietary nitrate to have these beneficial effects, it needs to be converted in the body to nitrite, via bacteria that live in the mouth (oral bacteria). Differences in oral bacteria, and how they metabolise nitrate, are thought to influence blood pressure regulation and potentially response to dietary nitrate supplementation. This study aims to understand (1) whether pregnant women with high blood pressure have a different composition of oral bacteria compared to healthy pregnant women and women who are not pregnant, and (2) how differences in oral bacteria affect blood pressure responses to a dose of dietary nitrate (in the form of beetroot juice).

Assessment of oral bacterial profile using next-generation sequencing (bacterial 16S rRNA sequencing)

Measurement of plasma and salivary nitrate and nitrite concentrations, using high-performance liquid chromatography (HPLC)

Correlation between salivary nitrate reductase activities and the change in salivary/plasma nitrite concentrations post-nitrate dose

Correlation between changes in plasma nitrite concentrations and blood pressure lowering post-nitrate dose

Inclusion Criteria: Normotensive or hypertensive women (hypertension as systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg OR on anti-hypertensive medication) For pregnant women, between 20-28 weeks gestation Exclusion Criteria: Multi-fetal pregnancy (for pregnant women) Age under 16, or over 45 years of age Lacking ability to consent Pre-existing diabetes (Type 1/Type 2) Previous history of pre-term FGR (delivery before 32 weeks with FGR) Current tobacco smoker Body Mass Index greater than or equal to 40 or less than or equal to 18 Use of any of the following drugs in the last 6 months: systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral) Large doses of commercial probiotics (greater than or equal to 108 cfu or organisms per day) including tablets, capsules, lozenges, chewing gum or powders (ordinary dietary components such as yoghurts do not apply) Evidence of oral disease, assessed on screening proforma (current conditions of: oral candidiasis (thrush); Dental caries (tooth decay); Halitosis; Oral ulcerations/mouth ulcers; Wisdom tooth pain; Chronic dry mouth) Allergy to beetroot juice or lemon juice (both contained within the juice shot)