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Health and Disease

The Health Benefits of Saliva

Unbeknownst to many, saliva has many purposes, both inside and outside of our mouths. Aside from it allowing for the mastication and swallowing of food, saliva from humans and other organisms have health benefits behind them.

Abstract

Unbeknownst to many, saliva has many purposes, both inside and outside of our mouths.  Aside from it allowing for the mastication and swallowing of food, saliva from humans and other organisms have health benefits behind them that, although not as common in practicing medicine. It can provide insight and access to possible solutions, in emergency settings and for future clinical use.  In this paper, we take a look at the underlying science and the hidden properties of saliva, and how they can be applied in medicine for a variety of health concerns and problems, minor and possibly major. 

Introduction

Saliva is an extracellular oral fluid that is taken for granted. It serves many roles for different species, ranging from reptilian venomous drops to acting as a glue in construction of birds’ nests, thus demonstrating to have a diverse variety of functions [1]. 

Saliva production is stimulated by the sympathetic and the parasympathetic nervous system, and produced in the salivary glands, which are formed of clusters of acini cells. Secretion is controlled by the salivary centre composed of nuclei in the medulla [1].  In the human body, its main function is the preparation of food, from beginning the process of chemical digestion, to acting as a lubricant to make it easier to swallow, and even acting as a chemical carrier to taste cells.

However, it plays many more roles such as encouraging healing of wounds and tissue repair, protection and lubrication of our mouth, contributing to the upkeep of oral health and water balance [2].  Despite coming into contact with an abundance of microorganisms and flora found in or on the body, saliva protects our body from most of it, thus acting as one of the body’s strongest defence systems [3].  In addition to this, saliva holds a lot of power in diagnostics of many health issues and conditions including but not limited to: acne, allergies, heart conditions, cancer, and more [4]. 

Saliva is composed of 99.5% water, a variety of electrolytes, including sodium, potassium, calcium, magnesium, bicarbonate, and phosphates, as well as immunoglobulins, proteins, enzymes, mucins, and nitrogenous products, such as urea and ammonia [5,6]. 

Analysis of several studies have confirmed the importance of saliva in maintaining a healthy oral environment but it can also be used for purposes outside of the oral cavity in addition [7]. 

Oral Health

The oral cavity, in an average human, is estimated to have possibly as many as 8 million cells, with over 500 million bacterial cells per mL. Thus it is important to upkeep oral health in order to prevent different dental and oral diseases, and avoid foul odours from breath [6]. 

Saliva as a fluid constantly flushes the oral cavity of food debris, and keeps the mouth relatively clean [4].  However, from the moment teeth start to erupt in the oral cavity, saliva provides protection to the teeth on a more molecular basis. While the crown of the tooth is fully formed structurally, as it erupts, it is crystallographically incomplete.  So an interaction with saliva provides a post-eruptive maturation through diffusion of ions including calcium, magnesium, phosphorus, and fluoride, in addition to other molecules into the surface enamel. This maturation decreases permeability and absorption, increasing the hardness of the surface enamel, which has been shown to increase defence against cavities [5, 8].  Proline-rich proteins, statherin, and cysteine-containing phosphoproteins provide protection by effectively binding calcium and helping to maintain saliva with a high saturation calcium phosphate salts. They bind to the surfaces of early crystal nuclei and delay crystal growth [5]. 

Cystatins, a family of cysteine-containing proteins, have a minor role in regulating calcium levels in saliva. It is supposed that the main action of cystatins might be to inhibit the pathogenesis of periodontal disease [6]. 

Xerostomia, also known as dry mouth, is when an individual doesn’t produce enough saliva.  This can cause several problems to the individual such as difficulty ingesting food, foul breath, and the damage and weakening of the teeth [9].  As the flow of saliva is halted as one sleeps, in order to not choke, masses of bacteria can accumulate in the mouth, causing morning breath.[4] Lysozyme, an antibacterial enzyme present in saliva, which lyzes bacteria, preventing the overgrowth of microbial populations in the mouth [4]. The lack of saliva makes chewing and swallowing also difficult which often begins to affect an individual’s health. In order to treat xerostomia, doctors may prescribe saliva substitutes, which although can provide some temporary relief for the lack of moisture within the oral cavity. Saliva stimulants, parasympathomimetic drugs, organic acid and even lozenges are often used to stimulate the production of saliva.

Dental cavities/caries begins with acid dissolution of tooth minerals, initiated by acidogenic microorganisms in dental plaque which has been exposed to fermentable carbohydrate.  Macromolecule proteins and mucins serve to cleanse, aggregate, and/or attach oral microorganisms and contribute to dental plaque metabolism [6].  Individuals with xerostomia are more susceptible to dental caries because of the loss of the many protective factors in saliva [10]. 

Proline-rich proteins are also present, that contribute to the formation of the enamel, the outermost layer of teeth, as well as a substance capable of killing microbes in the oral cavity [6]. 

One major role of saliva is its participation in the formation of the acquired enamel pellicle (AEP) which is a protective layer that forms over teeth. The composition of the AEP selectively determines the types of microorganisms which can attach to the oral mucosa, thus protecting the enamel from any harmful molecules and damage. Because of the fairly rapid turnover of the cells in the oral mucosa, it is not possible for thick layers of biofilm to accumulate on them. The AEP is primarily a protein layer which covers all surfaces of the enamel and the underlying dentine or cementum when these have become exposed by loss of enamel, although the presence of certain lipids has also been reported [11]. 

Wound Healing

Wound healing involves four overlapping phases: hemostasis, inflammation, proliferation, and tissue remodelling.  The mouth is susceptible to wounds of various types, ranging from cheek biting to tooth extraction, and saliva plays an important role in the healing of all wounds [12]. Notably, oral wounds heal much faster than skin wounds and with relatively much less scar formation as proven by studies on pigs, and some studies suggest it is due to the properties of saliva[13]. 

Saliva contains nerve growth factor and epidermal growth factor, which have been found to accelerate the rate of wound healing [5, 10, 14, 15].  

Levels of stress have been proven to alter saliva composition and are in correlation to reduce wound healing.  Saliva contains catecholamines (hormones produced by the adrenal glands) and keratinocytes (outermost skin layer). These keratinocytes contain receptors which when activated, impair oral keratinocyte migration.  As levels of stress increase, the higher levels of catecholamines, which may cause delayed healing by their inhibitory action on oral keratinocytes [10].

Tadokoro et al.  showed that leptin, an anti-obesity hormone present in saliva, promotes wound healing by stimulating angiogenesis, the production of new blood vessels [15].  Likewise in 1942 Volker demonstrated that saliva speeds up blood flow, coagulation which leads to scabbing, in the specific areas, ultimately providing protection [5, 16]. 

Histatins are histidine-rich proteins which have also been found to be contributors to wound healing as it promotes cell migration observed in the oral cavity [17,18].  They hold antibacterial and antifungal properties.  Histatine-1, histatine-2, and histatine-3 promote the migration of oral keratinocytes within in vitro wound closure, improving the re-epithelialization phase [19-21]. 

Antimicrobial Aspects

As well as a diagnosis tool, many salivary components have anti-fungal, antibacterial and antiviral properties [22]. 

ANTIVIRAL:

Saliva has been found to eliminate or reduce the presence of influenza A as well as HIV [22]. The protein, salivary agglutinin(gp340) is encoded by the dmbt1 gene and has been found to be anti-HIV.  In 1997 gp340 was proven to inhibit the virus by binding to gp120 on the surface of the virus [22].  HIV is deemed not transmittable via the oral route due to the antiviral properties being able to inhibit and kill the virus [23]. 

Mucins are complex antiviral proteins which act by aggregation and encapsulation. Similarly to cell membranes and as a big component of mucus, they act by selectively modulating the adhesion of the virus to the surface of oral tissue by trapping the virus, controlling how they can enter the tissue and the colonization of viruses.

Von Ebner glands protein (VEGh) is a cysteine proteinase inhibitor protein. VEGh belongs to the lipocalin superfamily, the members of which possess very similar structural features.  Lipocalin, which is identical to VEGh possess endonuclease activity which may act as an antiviral and inhibit of RNA and DNA viruses [24] 

ANTIBACTERIAL: 

Saliva contains lysozyme, lactoferrin, salivary lactoperoxidase, and immunoglobulin A (IgA), all of which are antibacterial enzymes. It also contains thiocyanate, hydrogen peroxide and secretory immunoglobulin, which are also antibacterial compounds [6, 25].  

Lactoferrin, produced in intercalated ductal cells, binds ferric iron in saliva. This process makes ferric iron unavailable as a food source for microbes including cariogenic streptococci, that need iron to live [6].  This process of restricting and starving bacteria of vital nutrients is called nutritional immunity [6]. Lactoferrin is also capable of a bactericidal effect that is distinct from simple iron deprivation [5]. 

Peroxidase, also known as sialoperoxidase or lactoperoxidase, catalyzes bacterial metabolic by-products with thiocyanate, which is highly toxic to bacterial systems [6, 26].  Secreted by acinar cells, peroxidase also protects mucosa from the strong oxidizing effects of hydrogen peroxide produced by oral bacteria [6]. Salivary peroxidase is part of an antibacterial system.  This system involves oxidising salivary thiocyanate with hydrogen peroxide which is generated by oral bacteria to hypothiocyanite and hypothiocyanous acid. These products, in turn, affect bacterial metabolism, particularly acid production, by oxidizing the sulfhydryl groups of the enzymes involved in glycolysis and sugar transport. The antimicrobial effect of salivary peroxidase against the bacteria S. mutans is increased by interacting with secretory IgA [5]. 

Immunologic contents of saliva include secretory IgA, IgG, and IgM. Nonimmunologic salivary contents are selected proteins, mucins, peptides, and enzymes [27].  Nonimmunologic antibacterial salivary contents such as proteins, mucins, peptides, lactoferrin, lysozyme, and peroxidase, protect teeth against physical, chemical, and microbes and threats [6]. 

Secretory IgA, the largest immunologic component of saliva, is an immunoglobulin produced by plasma cells in connective tissues and translocated through the duct cells of major and minor salivary glands. IgA, while active on mucosal surfaces, also acts to neutralize viruses, serves as an antibody to bacterial antigens, and works to aggregate or clump bacteria, thus inhibiting bacterial attachment to host tissues [6]. 

Proteins such as glycoproteins, statherins, agglutinins, histatins, and proline-rich proteins act by aggregating bacteria. Clumping the microorganisms reduces the ability of bacteria to stick to hard or soft tissue oral surfaces, spreading throughout the oral cavity and thereby controls bacterial, fungal, and viral colonization [6, 28].

 Although saliva has numerous antibacterial functions, it supports and contributes to the selective growth of bacteria and non-cariogenic microflora [6].  For example some probiotics including lactobacilli can fight harmful bacteria in the oral cavity and can help to heal gum disease, plaque buildup and inflammation [30].

Conclusion

From creating protective layers on the teeth, to increase scabbing for wound healing for preventative measures, and encapsulating and lysing bacteria and viruses in the mouth, saliva has far more health benefits and qualities that more than often go unnoticed.    In contrast to the common connotations of saliva within society being disgusting and offensive, saliva holds so much power within medicine, being a diagnostic tool, a protector and a healer. 

References

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[21] Oudhoff, M. J., Blaauboer, M. E., Nazmi, K., Scheres, N., Bolscher, J. G., & Veerman, E. C. (2010). The role of salivary histatin and the human cathelicidin LL-37 in wound healing and innate immunity. Biological chemistry, 391(5), 541-548. 

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[26] Tenovuo, J., & Knuuttila, M. L. (1977). Antibacterial effect of salivary peroxidases on a cariogenic strain of Streptococcus mutans. Journal of dental research, 56(12), 1608-1613. 

[27] Vila, T., Rizk, A. M., Sultan, A. S., & Jabra-Rizk, M. A. (2019). The power of saliva: Antimicrobial and beyond. PLoS pathogens, 15(11), e1008058 

[28] Thompson, R., & Shibuya, M. (1946). The inhibitory action of saliva on the diphtheria bacillus: the antibiotic effect of salivary streptococci. Journal of bacteriology, 51(6), 671. 

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[30] Baker, J. L., & Edlund, A. (2019). Exploiting the oral microbiome to prevent tooth decay: Has evolution already provided the best tools?. Frontiers in microbiology, 9, 3323.

By Nara Ito

Nara Ito is a student from London, England. She is interested in neurology, immunology, and genetics

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