Vegetable rich diets contain natural inorganic nitrate. These diets are linked to good heart and brain health. Human cells cannot 'activate' nitrate. Humans must rely on specific bacteria living in the mouth to digest nitrate to an active form called 'nitric oxide' that we can use in the body. We have found that nitrate makes the oral microbiome healthier and improves nitric oxide production. This study will investigate whether changes in oral bacteria caused by dietary nitrate are linked to any changes in brain performance.We will ask 60 healthy men and women of over 50 years of age to take part. We will ask them to drink either nitrate-rich beetroot juice or placebo juice daily for 12 weeks. We will do this investigation entirely remotely by using online tools and by posting of supplements and samples. We will sample the volunteers' oral microbiome and assess their cognitive performance before and after dietary supplementation. We will analyse the nitric oxide content in the samples that the volunteers post us. We will try to findgroups of bacteria linked with goodbrainfunction.The results will help us better understand how oral bacteria may influence cognitive function in older age.
Oral dysbiosis and poor dental health have been associated with impaired cardiovascular and cognitive health, but it is not known which characteristics of bacterial communities specifically might mediate such relationships. One mechanism by which the oral microbiota may influence health is its contribution to production of the signalling molecule, nitric oxide (NO), which, among many other functions, regulates vascular tone and neurotransmission . The capacity for endogenous NO production via the enzymatic NOS synthase pathway declines in older age, contributing to development of arterial hypertension, reduced physical and cognitive functional capacity, and increased morbidity. Therefore, the composition of the oral microbiota may be particularly important to enable older people to benefit from a nitrate-rich diets, such as the Mediterranean diet, which has been associated with reduced risk of developing dementia in older age. A key genetic risk factor for dementia is a form of apolipoprotein E gene called APOE4, which may also modulate responsiveness to dietary interventions.The purpose of this research is to investigate whether specific groups of oral bacteria, that are sensitive to change with dietary nitrate supplementation, are correlated with indices of cognitive function (primary objective) as well as APOE genotype, diet, physical activity, and markers of vascular health (secondary objectives), in people over 50 years of age.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
60
University of Exeter Sport and Health Sciences
Exeter, Devon, United Kingdom
Change from baseline oral bacteria co-occurrence at 12 weeks using oral microbiome abundance data and WGCNA analysis.
Identify co-occurring clusters of oral bacteria which are consistently related to indices of cognitive status across dietary interventions with nitrate and placebo. Using oral microbiome abundance data from sequenced oral microbiome DNA in the mouth rinse samples, the change from baseline to post-12 week intervention is measured. WGCNA analysis is used to cluster co-occurring bacteria and detect patterns of grouping.
Time frame: Change measured between baseline and 12-weeks post-intervention.
Change from baseline oral nitric oxide bioavailability at 12 weeks using ozone-based chemiluminescence.
The change from baseline to post-12 week intervention nitrate and nitrite concentrations in mouth rinse samples is measured using ozone-based chemiluminescence.
Time frame: Change measured between baseline and 12-weeks post-intervention.
Change from baseline composition of the oral microbiome at 12 weeks using oral microbiome abundance data from sequencing oral microbiome DNA in mouth rinse samples.
Oral microbiome sequencing of bacterial DNA isolated from mouth rinse samples. The change in the composition of the oral microbiome is measured from baseline to post-12 week intervention using oral microbiome abundance data.
Time frame: Change measured between baseline and 12-weeks post-intervention.
Change from baseline cognitive status at 12 weeks.
'Factors of Longitudinal Attention, Memory and Executive Function' (FLAME) composite score. Online FLAME cognitive assessment battery completed at home by the participants via the online PROTECT study. The FLAME cognitive assessment is a validated battery of online cognitive tests where correct/incorrect responses and response time are measured.
Time frame: Change measured between baseline and 12-weeks post-intervention.
Correlation between oral microbiome and existing descriptive data.
Correlation of oral microbiome with existing PROTECT cohort variables (APOE genotype, diet, physical activity). The oral microbiome abundance data is correlated with APOE genotype and dietary and physical questionnaire data.
Time frame: Correlation measured after 12-weeks post-intervention.
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