Abstract

Metabolomic profiling of biofluids, e.g., urine, plasma, has generated vast and ever-increasing amounts of knowledge over the last few decades. Paradoxically, metabolomic analysis of saliva, the most readily-available human biofluid, has lagged. This review explores the history of saliva-based metabolomics and summarizes current knowledge of salivary metabolomics. Current applications of salivary metabolomics have largely focused on diagnostic biomarker discovery and the diagnostic value of the current literature base is explored. There is also a small, albeit promising, literature base concerning the use of salivary metabolomics in monitoring athletic performance. Functional roles of salivary metabolites remain largely unexplored. Areas of emerging knowledge include the role of oral host–microbiome interactions in shaping the salivary metabolite profile and the potential roles of salivary metabolites in oral physiology, e.g., in taste perception. Discussion of future research directions describes the need to begin acquiring a greater knowledge of the function of salivary metabolites, a current research direction in the field of the gut metabolome. The role of saliva as an easily obtainable, information-rich fluid that could complement other gastrointestinal fluids in the exploration of the gut metabolome is emphasized.

Highlights

  • Saliva is a biological fluid produced in the oral cavity by three pairs of major glands and up to one thousand minor glands

  • Fluid produced by the parotid glands is termed parotid saliva (PS), and fluid produced by the submandibular gland and sublingual gland is typically described together as submandibular/sublingual (SM/SL) saliva

  • Protons (1 H) are the most common NMR-active nuclei studied in salivary metabolomics NMR spectroscopy, other nuclei such as 13 C are analyzed in heteronuclear two-dimensional studies

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Summary

Introduction

Saliva is a biological fluid produced in the oral cavity by three pairs of major glands and up to one thousand minor glands. Chewing and taste stimulation are both common approaches to increase salivary flow rates, in practice many studies elect to collect saliva passively, by spitting or drooling into a container as the fluid is produced in the mouth. Parotid gland saliva is most commonly collected with the use of a Lashley cup, while submandibular and sublingual gland saliva are typically collected together by pipetting methods and minor gland saliva can be collected using filter papers or capillary tubes [11] Despite advantages such as ease of collection and preparation, saliva is considerably less studied by metabolic profiling compared to fluids such as urine and plasma, as evidenced by the number of research outputs on the respective fluids [12]. With respect to MS-based studies, while there is a history of applying the technology to saliva for the targeted detection of analytes such as exogenous drugs and their metabolites, comprehensive profiling of saliva by MS emerged in the early 2010s [22,23]

Approaches to the Study of Salivary Metabolites
Current Knowledge of the Salivary Metabolome
Potential Physiological Significance of Salivary Metabolites
Future Directions for Salivary Metabolomics
Findings
Conclusions
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