Saliva has one of the most difficult roles to perform in the body. It must facilitate the taste and detection of foods nutritious to the body but also defend the mucosa from infection by the ever-present microbiota present in the mouth. It achieves these roles by having a complex composition and versatile physical properties. The protein and ion components make a solution that is 99% water into a viscoelastic solution capable of many roles, such as acting as a lubricant and an antimicrobial, preventing the dissolution of teeth, aiding digestion, and facilitating taste. This review describes the neural regulation of salivary secretion in terms of fluid, protein, and ion secretion. It then describes some of the components and physical properties of saliva and attempts to relate them to the functions that saliva must perform.

Maintenance of a film of saliva on oral surfaces is dependent upon nerve-mediated, reflex salivary gland secretion. Afferent signalling arises from taste, olfaction and mastication and is modified by signalling from other centres in the central nervous system before efferent signals are delivered to salivary glands in autonomic nerves. Salivary fluid secretion is largely dependent upon cholinergic signalling from parasympathetic nerves whilst the protein content of saliva is additionally dependent upon signalling by neuropeptides and, in the major (parotid, submandibular and sublingual) salivary glands, by sympathetic nerves and the release of noradrenaline. There have been significant recent advances in our understanding of the membrane transport proteins involved in intracellular calcium signalling in salivary acinar cells in response to nerve stimulation and of the ion transport proteins responsible for acinar cell secretion of saliva. Salivary glands retain an ability to regenerate following extreme atrophy, and autonomic nerves have an important role in both gland development and maintenance of long-term normal function. Continued advances in the understanding of the nerve-mediated regulation of salivary glands should help in the development of strategies for preventing chronic oral dryness resulting from drugs or atrophic disease associated with inflammation and irradiation.

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.