The human alimentary canal hosts a major microbial ecosystem and the metabolic outputs of these microbes make a significant contribution to host physiology. The symbiotic role of the gut microbiota as a modulator of physiological and cognitive health is well-established [1,2] and cross-sectional studies indicate that a perturbed oral microbial community and poor dental health are associated with impaired cardiovascular and metabolic health . However, relatively little is known about the mechanisms that underlie the host-oral microbiota axis as a potential modulator of human health. One mechanism by which the oral microbiota may influence human health is its contribution to the production of the signalling molecule nitric oxide (•NO), which regulates vascular tone, mitochondrial respiration and neurotransmission among many other functions [, , , ].
Some facultative and obligate anaerobic oral bacteria reduce nitrate to bioactive nitrite, a key precursor to •NO . Vegetable-rich diets, such as the Mediterranean and ‘Dietary Approaches to Stop Hypertension’ (DASH) diet, are abundant in dietary nitrate and oral bacteria play a key role in the pathway of •NO production from such dietary nitrate. This is particularly important in older age, where the capacity for endogenous •NO production via the canonical enzymic •NO synthase pathway has declined [9,10]. Low •NO availability contributes to the development of arterial hypertension, reduced physical and cognitive functional capacity, and increased morbidity [11,12]. The important role of oral bacterial nitrate reduction as a parallel pathway for endogenous •NO production is demonstrated by studies showing that use of bactericidal mouthwash acutely reduces systemic •NO bioavailability and elevates blood pressure [13,14], and that chronic, frequent use of mouthwash is associated with elevated risk for type II diabetes . Conversely, increased consumption of dietary inorganic nitrate elevates •NO bioavailability and reduces blood pressure [, , ], improves skeletal muscle contractility [19,20] and exercise efficiency [21,22], and enhances brain perfusion and cognitive function [23,24]. Elevation of •NO bioavailability via dietary means, therefore, potentially represents a powerful therapeutic to attenuate cognitive and cardiovascular decline associated with aging .
Inorganic nitrate is emerging as an effective intervention to alter the oral microbiome. As a prebiotic dietary intervention, nitrate appears to increase the abundances of bacteria belonging to Neisseria and Rothia genera [, , ] and decreases abundances of Prevotella and Veillonella species .
The purpose of this study was to determine 1) which co-occurring modules of bacteria in the salivary microbiome of healthy older people were sensitive to dietary nitrate intake, 2) which co-occurring oral microbiome modules correlated with cognitive and physiological traits across dietary interventions with placebo and nitrate, and, 3) which nitrate-sensitive modules represent key biomarkers, and thus probiotic targets, for enhancing cardiovascular and cognitive health. We established eight distinct modules of co-occurring bacteria and revealed profound alterations in relative abundances of specific members of these clusters following dietary nitrate supplementation. We identified several significant correlations between oral bacteria modules and indices of cognitive and physiological function, which represent promising avenues for translational research into biomarkers and therapies for cognitive and cardiovascular impairment in older age.