Abstract
Metabolomics is the study of the small molecules that are present within a biological sample or system. Metabolomic analysis is yielding ever-increasing new information about the role of metabolites in health and disease. Much of the literature to date has focused on biofluids such as urine or plasma although saliva is increasingly being identified as an important fluid for metabolomic study. Functional roles for metabolites generated in the gut are being discovered, in relation to both health and disease, however little is known about the role(s) salivary metabolites play in health. Taste perception is an important physiological process occurring in the oral cavity that has wide reaching implications for health and it has been speculated that the metabolic composition of saliva may influence taste perception.This thesis explores the metabolic composition of saliva with particular emphasis on relationships with taste perception and other oral sensations such as astringency. Other questions that are addressed include the role of the oral microbiome in shaping the metabolic composition of saliva and the association between the metabolic composition and physical properties of saliva. The main analytical platform for metabolomic profiling of saliva was proton nuclear magnetic resonance spectroscopy (1H-NMR).
In the first instance, validation of the analytical and sensory methodologies adopted throughout this thesis were conducted, to satisfy that subsequent data gathering was valid. It was then found, through a combination of in-vivo and in-vitro analyses, that the salivary metabolome is largely shaped by oral bacteria. The most concentrated salivary metabolites such as the short chain fatty acids (SCFAs) acetate, butyrate and propionate are of microbial origin whereas metabolites such as lactate, citrate and urea are of host origin. Furthermore, oral bacteria were shown in-vitro to catabolise salivary proteins and endogenous metabolites, generating abundant SCFAs and other salivary metabolites. Modulating effects of gustatory reflexes on salivary metabolic composition were then investigated for sucrose (sweet), caffeine (bitter), menthol (cooling) and capsaicin (warming). Sucrose was found to be rapidly catabolised by oral bacteria, generating abundant metabolites such as pyruvate and lactate, whereas capsaicin stimulation increased citrate concentrations. Citrate was also found to relate to the extensional rheology of capsaicin-stimulated saliva.
Assessment of the relationship between taste perception and salivary composition was approached from two angles. Firstly, taste recognition and detection thresholds were assessed in a taste panel. A positive association between salivary urea and sucrose detection threshold was discovered. As urea was found to be consumed by oral bacteria, inversely correlating with salivary bacterial load, it is speculated that differences in salivary urea between sensitive and insensitive glucose detectors might reflect differences in the composition and/or function of the oral microbiome. Additional findings relating to the salivary metabolome that stemmed from this thesis include an apparent lack of any significant genetic contribution to the salivary metabolome and a significantly higher degree of intraindividual stability compared to inter-individual stability of salivary metabolite profile.
Subsequently, suprathreshold taste perception of sucrose, aspartame, caffeine, black tea and oleic acid (sweet, sweet, bitter, astringent, fatty; respectively) and salivary composition was assessed in a twin study. Generally, twins with discordant tastes as well as unrelated individuals with different tastes has similar differences in their saliva composition. Twins with similar levels of taste perception did not display these salivary differences. Invariably, these relationships were inverse i.e. higher metabolite concentration was associated with reduced taste sensitivity. Salivary composition therefore appeared to be an important local environmental factor in determining sensitivity to certain taste stimuli. Controlling for salivary flow rate also emerged as important, as higher flow rate was associated with lower metabolite concentrations and improved sensitivity. This suggested that the degree to which salivary fluid dilutes microbial-produced metabolites in the mouth may impact on taste perception. There was no evidence of a general inhibitory metabolite across the different tastants although taurine was associated with both sucrose and oleic acid perception.
Collectively, this work found that the salivary metabolome represents a complex balance between host and microbial metabolic activity. It can be concluded that there is evidence of associations between salivary metabolite composition and taste perception. Certain metabolites of microbial origin were inversely associated with taste perception, and an endogenous metabolite known to be consumed by oral bacteria (urea) was positively associated with sucrose detection. The findings of this work support the emerging role of metabolomics as a functional measure of complex microbial communities in relation to host physiology. While the findings of this work cannot be used to infer a causal relationship between specific metabolites and taste, target salivary metabolites for future study in association with taste perception are identified.
| Date of Award | 1 May 2020 |
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| Original language | English |
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| Supervisor | Guy Carpenter (Supervisor) & Po-Wah So (Supervisor) |