ISSN: 2320-5407 Int. J. Adv. Res.

12(06), 1214-1224

Journal Homepage: - www.journalijar.com

Article DOI: 10.21474/IJAR01/18986

DOI URL: http://dx.doi.org/10.21474/IJAR01/18986

RESEARCH ARTICLE
SALIVARY BIOMARKERS OF DENTAL CARIES - A REVIEW ARTICLE

Dr. Madhuri Gupta, Dr. Shipra Jaidka, Dr. Deepti Java, Dr. Bhuvan Deep Gupta, Dr. Sujata and Dr. Apurva
……………………………………………………………………………………………………....
Manuscript Info Abstract
……………………. ………………………………………………………………
Manuscript History Saliva is the complex mixture of fluids that surrounds the oral tissues,
Received: 25 April 2024 secreted by the major and minor salivary glands1. Human saliva not
Final Accepted: 28 May 2024 only lubricates the oral tissues, making oral functions such as speaking,
Published: June 2024 eating, and swallowing possible, but also protects teeth and oral
mucosal surfaces in different ways. Dental caries is recognized as a
Key words:-
Saliva, Biomarkers, Dental Caries, pH, multi-factorial infectious disease caused by complex interactions
Buffering Capacity among acid-producing bacteria, fermentable carbohydrates and many
host factors including saliva. Saliva is easy to collect, to store, and can
be obtained at low cost in sufficient quantities for analysis by a non-
invasive method. Thus it has the potential to be used in the early
detection and diagnosis of various oral diseases due to the abundant
biomarkers present in saliva. Saliva biomarkers such as salivary flow,
salivary pH, salivary proteins, microorganisms etc, are used for the
prediction, diagnosis, prognosis and management of dental caries, as
well as for evaluating the outcome of therapeutic regimens. This article
aims to providea brief overview of salivary biomarkers present which
can be used for the early detection nd prevention of dental caries in
humans.

Copy Right, IJAR, 2024,. All rights reserved.

……………………………………………………………………………………………………....
Introduction:-
Saliva is considered to be the “mirror of our body” as it is an indicator of general health not just the oral cavity.
Saliva is the complex mixture of fluids that surrounds the oral tissues, secreted by the major and minor salivary
glands1. Human saliva not only lubricates the oral tissues, making oral functions such as speaking, eating, and
swallowing possible, but also protects teeth and oral mucosal surfaces in different ways. The resting saliva maintains
the lubricating and antimicrobial functions of saliva. Stimulation of saliva results in a flushing effect and the
clearance of oral debris and noxious agents2.

Saliva as a biological fluid serves as the diagnostic tool in health and disease for more than 2000 years 3. It can be
used as a diagnostic tool in various systemic diseases like hereditary disorders, autoimmune diseases, infectious
diseases, as well as in the assessment of therapeutic levels of drugs and monitoring of illicit drug use, and also for
forensic evidence and others.

Most importantly saliva plays a great role in diagnosis of oral diseases like dental caries, periodontal disease and
oral cancer. In the last few decades, there has been a focus on the utilization of saliva for microbiological tests that
give an indication of dental caries.

Corresponding Author:- Dr. Madhuri Gupta

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Dental caries is recognized as a multi-factorial infectious disease caused by complex interactions among acid-
producing bacteria, fermentable carbohydrates and many host factors including saliva 4. Dental Caries is the most
prevalent oral disease in Asian and Latin American countries, while it appears to be less common and less severe in
most African countries5. It remains a major health issue in the United States and worldwide with a prevalence of
more than 40 percent in young children and about 90 percent in the adult population5.

Saliva biomarkers such as salivary flow, salivary pH, salivary proteins, microorganisms etc, are used for the
prediction, diagnosis, prognosis and management of dental caries, as well as for evaluating the outcome of
therapeutic regimens6. The salivary flow is important in the prevention of caries, and there is a high risk of caries in
individuals with a low unstimulated salivary flow. All salivary functions, such as buffering and clearance are
dependent on the salivary flow rate.

There are certain epidemiological studies which have shown that children who experience colonization by mutans
streptococci early in life are at greater risk of developing dental caries than those who are colonized later7,8. A study
of oral Candida species suggest their cariogenic potential since they exhibit acidogenic hetero fermentative
properties, especially in the presence of carbohydrates, and co aggregation with other bacteria in biofilms 4.

These studies help us to understand the role of salivary biomarkers in prediction of dental diseases. The saliva is
recognized as one of the important factor which helps in preservation and maintenance of oral and systemic health
irrespective of its quantity whether large or small9 . Hence this article aims to to provide an overview of the current
understanding of the salivary biomarkers which are used for the prediction, diagnosis, prognosis and management of
dental diseases.

History
From the Australopithecines (over a million years ago) to the Neolithic (since 10,000 years ago), carious lesions
have been found in almost every population studied. Caries, however, was very uncommon amongst fossil hominids
into the Paleolithic and Mesolithic. A Sumerian text from 5000 BC describes a tooth worm as a cause of caries10.
The EbersPapyrus ,an Egyptian text from 1550, mentions diseases of teeth. The rate of caries remained low through
the Bronze age and Iron age, but sharply increased during the Middle ages. During the Roman occupation of Europe,
wider consumption of cooked foods led to a small increase in caries prevalence 11.

The prevalence of caries increased dramatically in the 19 th century, as the Industrial revolution made certain items,
such as refined sugar and flour, readily available. In the 1890s W.D.Miller gave chemo parasitic caries theory. This
lead to need of proper diagnosis and treatment of dental caries12.

Some decades ago, visual examination (light and mirror) and probing, supplemented by bitewing radiographs were
the only tools available for clinical diagnosis of caries. However a variety of innovative technologies have been
developed and introduced in the last few years to aid clinicians not only in early diagnosis of caries but make a firm
diagnosis and to treat cases conservatively. Salivary diagnostic is one of these recent advancements.

Saliva contains the serum constituents that can be used as a diagnostic tool in various diseases like hereditary
disorders, autoimmune diseases, infectious diseases, as well as in the assessment of therapeutic levels of drugs and
monitoring of illicit drug use, and also for forensic evidence and others. Moreover saliva also plays a great role in
diagnosis of oral diseases like dental caries, periodontal diseases and oral cancer. Bacteriological tests of saliva
plays the most important role in prediction of dental caries which is recognized as a multifactorial infectious disease
caused by complex interactions among acid producing bacteria ,fermentable carbohydrates and many host factors
including saliva .

Salivary biomarkers such as salivary flow, salivary pH salivary proteins, micro organismsetc, are used for
prediction, diagnosis, prognosis and management of dental caries, as well as for evaluating the outcome of
therapeutic regimens.

Discussion:-
Saliva is an exocrine secretion of the salivary glands mainly composed of water 99%, but it also contains
electrolytes proteins, lipids and enzymes, Contaminants such as bacteria, epithelial cells, and gingival crevicular
fluid and food debris are also detectable in saliva. These all can be used for diagnostic as well therapeutic purpose

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for many diseases. All physical and chemical properties of saliva can also be used for screening, diagnosing and
prognosing of multiple local and systemic health problems. The use of saliva as an alternative diagnostic tool is
advisable since its collection is non invasive and possibly stress-free. Furthermore a large amount of saliva can be
easily collected and stored with non invasive and cost saving procedures13.Development of sensitive and precise
salivary diagnostic tools and the formulation of defined guidelines following meticulous testing will allow salivary
diagnostics to be utilized as chair side tests for various oral and systemic diseases in the near future.

Brief Overview of Saliva

Saliva is composed of a variety of electrolytes, including sodium, potassium, calcium, magnesium, bicarbonate,
and phosphates11. Immunoglobulins, proteins, enzymes, mucins, and nitrogenous products, such as urea and
ammonia are also found in saliva.

Flowchart 1:- Composition of saliva.

Stimulated Vs Unstimulated Saliv14

Saliva can be collected from specific salivary glands or sampling whole saliva. In both cases, the samples have the
same chemical composition, although the concentration of analytes can vary.

Unstimulated whole saliva-

It is the mixture of secretions that enters the mouth in the absence of exogeneous stimuli and depends on the daily
basal salivary flow rate in the oral cavity49.The sampling of unstimulated saliva is often preferred because it
minimizes the dilution of analytes.

Stimulated saliva-
It is physiologically secreted in response to either masticatory or gustatory stimulations during food intake. Its
composition depends on the gland size, food intake, smoking, gag reflex and type of stimulation given. Various
stimulants such as paraffin wax, unflavored chewing gum base, cotton puff and rubber bands can be used to sample
saliva by masticatory stimulation, whereas gustatory stimulation can be obtained using citric acid and sour candy
drop

Biomarkers can be identified in both stimulated and unstimulated saliva. The sampling of unstimulated saliva is
often preferred because it minimizes the dilution of analytes.

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Methods of Saliva Collection14:-

There are many simple and non invasive methods to collect saliva to study biomarkers.
1. Passive drooling and draining method- Passive drooling is usually performed by asking the subject to "deburr"
(let the saliva drop) into plastic tubes (e.g. polypropylene) with the head tilted forward.
2. Spitting - Spitting is the accumulation of saliva in the floor of the mouth followed by spitting it into a preweighed
or graduated container, e.g. a funnel connected to a tube/container.
3. Swab-based sample - Whole saliva can be sampled by placing swabs or other absorbent materials in the mouth.
The choice of the material should depend on the subject‟s tolerability (dimensions, taste and allergy).

Advantages Of Saliva As A Diagnostic Fluid15

1. Noninvasive diagnosis of disease and monitoring of general health.
2. Painless, patient suffers no discomfort and little anxiety in the collection process.
3. Simple in collection with a modest trained assistant and applicable in remote areas.
4. Relatively cheap technology as compared to other tests.
5. Cost effective applicability for screening large population.
6. Can be used to study special population where blood sampling is a problem e.g. children, anxious /handicap/
elderly patients.
7. Convenient for multisampling.
8. Safer for health professionals than blood tests.
9. Compared to blood and urine, saliva is also cheaper to store and ship.
10. In addition saliva does not clot and can be manipulated more easily than blood.

Limitations Of Saliva As A Diagnostic Fluid 15

1. Disparity between salivary and serum biomarkers.-Biomarkers in the blood are commonly measured in
micrograms which is one –millionths of a Gram. Biomarkers in saliva are commonly measurable in pictograms,
one trillionth of a Gram ,ornanogram and so have to be very meticulously identified and assessed.
2. Technique sensitive-Absorbent devices may collect localized saliva rather than whole saliva which may affect
results for some analytes. Head position also can affect pooling of saliva.
3. Effect of change in salivary flow rate-Most hormones display a diurnal rhythm of expression, and this can be
true for certain salivary proteins as well.
4. Variability among individual- The biologic variation (BV) can be intraindividual variability which can be due
to cyclical variations (circadian, monthly, or seasonal) or inter individual variations over the lifespan of the
individuals (e.g., age-related hormonal changes).
5. Contamination with serum-Many serum markers can reach whole saliva in an unpredictable way (i.e. gingival
crevicular fluid flow and through oral wounds) and can affect the diagnostic usefulness of many salivary
constituents.
6. Effect of systemic disorder-The quantity and composition of saliva get affected by systemic disorders (Sjogren
syndrome, viral infections, uncontrolled diabetes, hypertension & depression),numerous medications and
radiation.

Saliva and Caries Risk16

Caries is a complex phenomenon involving internal defense factors, such as saliva, tooth surface morphology,
general health and nutritional and hormonal status, and a number of external factors-for example, diet, the
microbial flora colonizing the teeth, oral hygiene, and fluoride availability. 2

Normal salivary output, as quantified by flow rate, is an extremely important intrinsic host factor providing
protection against caries, and that pathologically diminished flow rate is a significant risk factor for caries
development. Salivary low buffering capacity, low calcium and phosphate, and low specific sIgA show a less
pronounced link to increased caries. There is no association with caries risk for salivary pH, other electrolytes or
small molecules, total sIgA, IgG, IgM, and other salivary proteins, including those of the innate host defense
system. This lack of correlation is due to the multiple levels of structure-function redundancies found in saliva16
(Table 1).
Strong Weak-to-Moderate Association
Association with Caries Risk No Association with Caries Risk
with Caries
Risk

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Flow Rate Buffering Capacity; pH (static measurement);

Calcium/Phosphate; Glucose Clearance
Specific Rate/Concentration; Other Electrolytes &
sIgAImmunog Small Organic Molecules; Total sIgA; IgG,
lobulin IgM, Innate
Immunity Factors

Some important characteristics of saliva which can be used as salivary biomarkers for dental caries are as
follows:
1. Functional bio markers of saliva
2. Microbial bio markers
3. Electrolytes
4. Salivary Proteins

Functional Biomarkers of Saliva for Dental Caries:17

1. Salivary flow rate
2. Saliva pH and buffering capacity

Salivary Flow Rate:

Saliva plays a significant role in maintaining oral health, helping to build and maintain the health of soft and
hard tissues. When saliva flow is reduced, oral health problems such as dental caries and oral infections can
develop18.

Unstimulated Saliva Flow Rate:

At rest, without exogenous or pharmacological stimulation, there is a small, continuous salivary flow,
aunstimulated secretion, present in the form of a film that covers, moisturizes, and lubricates the oral tissues.
This flow of saliva at rest is in the region of 0.4- 0.5mL/minute in healthy subjects 18, 19

MAJORFACTORS MINORFACTORS
Degree of hydration Gender
Body position Age(above15years)
Exposure to light Body weight
Previous stimulation Gland size
Circadian rhythms Psychic effects-thought/sight of food
Circannual rhythms Functional stimulation

Stimulated Saliva Flow Rate:

Stimulated saliva is produced in response to a mechanical, gustatory, olfactory, or pharmacological stimulus,
contributing to around40-50% of daily salivary production.

Nature of stimulus Glandsize

Mechanical Unilateral stimulation
Gustatory Vomiting
Pharmacological Olfaction
Food intake Smoking
Gag reflex

Clinical Significance of Salivary Flow Rate:

Practically all other salivary functions, such as buffering and clearance, depend on the salivary flow rate.
Cavities are most prevalent in patients with a lower salivary flow due to a decrease in the antibacterial,
buffering and cleansing functions. The salivary flow dilutes the substances, cleans the oral cavity of
carbohydrates, non-adherent bacteria18, desquamated epithelial cells and food debris. This phenomenon is
essential for decreasing the availability of sugars for the bio film. The salivary viscosity reduces the hydration
capacity of saliva, and consequently raises the caries risk. People with low salivary flow are often, but not
always, related to caries susceptibility and activity.

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Saliva pH and Buffering Capacity:

The pH of dental plaque is a key factor in the balance between acid demineralization of the teeth and the
demineralization of the initial caries lesion. Plaque pH falls each time acid accumulates in the plaque due to
bacterial acid production following the consumption of fermentable carbohydrates mainly sugars in foods and
drinks. Conversely, plaque pH rises when the acids are washed away or neutralized by saliva, which contains
the important buffer, bicarbonate. 18

Saliva has a pH normal range of 6.2-7.6 with 6.7 being the average pH. Resting pH of mouth does not fall
below 6.3.

Saliva has two main buffersystems:17

1st is the carbonic acid-bicarbonate system is the most efficient in stimulated saliva
2nd is phosphate buffer system which is efficient in unstimulated saliva.

Bicarbonate in saliva serves as the main buffer against acid, working in conjunction with the phosphate and the
protein buffersystems.17

Microbialbiomarkers of Saliva for Dental Caries17

Cariogenic bacteria are usually present in relatively small quantities in healthy saliva and plaque. However,
with biological and environmental changes such as the increased frequency of fermentable carbohydrate
consumption, conditions of low pH will favor the proliferation of bacteria.

The „specific plaque hypothesis‟ proposes a few specific species of bacteria as being responsible for caries,
the „ecological plaque hypothesis‟ considers caries as an outcome of the overall activity of a heterogeneous
mixture of microorganisms and a cariogenic shift of the plaque micro biomes. The acidic metabolites by
microorganisms cause a local pH fall below a critical value (pH 5.5) resulting in the demineralization of the
tooth tissue.17

Mutansstreptococciandlactobacilli
The main responsible bacteria for this disease are the endogenous strains Streptococcus mutans,
Streptococcus sobrinusand Lactobacillus species, present in the biofilm. Among various species, S.
mutanshas been identified as a strong pathogen for caries; however, other species, such as S. sobrinus, may
also play a minor role.8 Early acquisition of S.mutansis associated with early childhood caries and future
caries.17

1. Streptococcus mutans:S. mutansis able to metabolize a number of sugars and glycosides such as glucose,
fructose, sucrose, lactose, galactose, mannose, cellobiose, glucosides, trehalose, maltose and a previously
unrecognised, group of sugar-alcohols. In the presence of extra cellular glucose and sucrose,
S.mutanssynthesizes intracellular glycogen-like polysaccharides21
2. Lactobacilli:Lactobacilli are isolated from deep caries lesions but rarely just before the development of
dental caries and in the early tooth decay. It is believed that they are pioneering microorganisms in the caries
progress, especially in dentin. 21

As a late colonizer, lactobacilli may not be a requisite for caries initiation. However, they may potently
contribute to caries progression once lesions are established. As the level of lactobacilli in saliva also appears
to reflect the acidogenic conditions associated with the consumption of abundant simple carbohydrates, it
could serve as a useful indicator for a cariogenic diet.17

Salivary Electrolytes As Biomarkers For Dental Caries

Among the main salivary electrolytes, sodium, fluoride, chloride, calcium, phosphate and bicarbonate are
considered of particular importance for protecting teeth from caries. The presence of fluoride in saliva is very
important because it reduces acid production in the biofilm. Fluoride, calcium and phosphate ions keep saliva
supersaturated with respect to hydroxyapatite and offer a reparative and protective environment for
maintaining the integrity of dental tissues.

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Calcium
Clinical Consideration22 –
1. Increase in salivary calcium levels has a beneficial effect by remineralising the tooth enamel but
detrimental effect by remineralising the dental plaque that could favor the progression of periodontal
diseases by formation of calculus.
2. Decrease in salivary calcium level makes the plaque more acideogenic which may result in
demineralization of the enamel and more prone to dental caries.

Phosphate
Clinical Consideration23 –
1. If the phosphate levels are too high it can remove calcium from the bones which make them brittle
2. The low levels of phosphate concentration in saliva impacts protection and rebuilding of tooth enamel.
Teeth can chip easily .

Mechanism of action of Calcium and phosphate:

Calcium and trivalent phosphate (PO43-) ions, along with hydroxyl ions, maintain the saturation of saliva with
respect to tooth mineral, and are therefore important in calculus formation and in protecting against the
development of both caries anderosion24.

The equilibrium between calcium and phosphate ions in saliva and hydroxyapatite of the tooth is important to
maintain the tooth structure. Under acidic conditions free hydrogen ions reacts with hydroxyl and phosphate
ions forming water and mono hydrogen phosphate respectively, this affects the equilibrium between the solid
and ionic phases and as a consequence calcium ions from apatite are released. The hydroxyapatite crystals will
continue to dissolve until saturation is achieved or the pH rises.

Fluoride
Clinical Consideration24 –
1. If the fluoride levels are more than 1.5 ppm it can cause dental fluorosis which can cause changes in the
appearance of tooth enamel
2. Whereas <0.3 ppm of fluoride concentration in saliva impacts the activity of remineralisation.

SALIVARY PROTEINS (PROTEOME) AS BIOMARKER FOR DENTAL CARIES

The salivary proteome is composed mainly of salivary proteins and salivary peptides 21.

Antimicrobial Salivary Protiens

Major SalivaryProteins:
Major salivary glycoproteins such as mucin, immunoglobulin etcare involved in the first line of defense of
oral cavity25.

Minor Salivary Proteins:

Besides the major proteins, which account for approximately 50% of its total protein, saliva contains a number
of antimicrobial proteins that are present in lower concentrations. A number of these are enzymes which even
in low concentration can exert significant biological activity. Examples of antimicrobial proteins with enzymic
activity are lactoperoxidase and lysozyme etc. 25

Protective Properties of Salivary Proteins

Saliva is composed by various proteins with antimicrobial activity.Changes in salivary proteome can provide
changes in microbial flora, and consequently lead to caries progression. 17
SALIVARYPROTEIN PROPERTIES
Cystatins / VEGh Protease inhibitor
Immunoglobulins Inactivation and aggregation of bacteria
Lactoferrin Growth inhibition
Lactoperoxidase Growth inhibition
Lysozyme Killing
Proline- rich proteins(aPRPs) Adherence

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Proline- rich proteins(bPRPs) Unknown: membrane disturbing

Statherin Adherence

Protective action of salivary proteins against dental caries

Saliva comprises different components. The parotid gland secretes lysine and arginine. Cadaverine and
ammonia produced from lysine and arginine, respectively, neutralize the acidic environment generated by
sugar processing and lower dental caries' risk. In addition, saliva contains some enzymes such as amylase,
other proteins like histamines, some cystatins, and antibodies that act as antibacterial agents and inhibit
bacterial growth and reduce the risk of dental caries24(Fig 1)

Fig 1:- Protective action of salivary proteins against dental caries.

Antimicrobial Salivary Peptides

In saliva at least three types of antimicrobial peptides can be distinguished: histatins, defensins and
hCAP18/LL37, a human cathelicidin. Of these antimicrobial salivary peptides, the histatins are of utmost
importance.

Protective Properties of Salivary Peptides

These antimicrobial peptides have a broad antimicrobial activity not only against bacteria, but also against
yeasts. Such peptides can be used as templates to develop a new generation of antibiotics, because they work
very rapidly and efficiently, while they are negligibly cytotoxic and do not evoke resistance 19(Table 2 ).

Salivary Peptides Properties

CathelidinLL3 Antimicrobial activity
Histatins Antifungal and antibacterial
DefensinvHNP1-3 Anti viral activity
Beta-defensins hBD1 hBD2 hBD3 Microbial activity and anti viral properties
Statherin Remineralization of enamel

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The Various Salivary Proteins:

1.Immunoglobulin‟s
Immunoglobulin or antibodies are glycol proteins produced by plasma cells. There are 5 types of Immunoglobulin
in human25The immunoglobulin in saliva primarily belong to the IgA subclass (>85%).

Anti Caries Properties of Immunoglobulin 25

1. They play an antibacterial role by inhibiting bacterial metabolism, neutralizing bacterial toxins and
enzymes and agglutination of bacteria.
2. It promotes the inhibition of bacterial adherence, by the reduction of the hydrophobicity of bacteria.
3. It acts synergistically with other defense mechanisms, such as the lactoferrins, peroxidases, agglutinins and
mucins.

Proline-rich proteins17
Proline-rich proteins are a class of intrinsically unstructured proteins that contain several repeats of a short proline-
rich sequence. Proline-rich proteins can be divided into acidic and basic families.
1. The acidic proline-rich proteins adheres strongly to recently cleaned tooth surfaces. Acidic proline-rich
proteins account for 25-30% of all proteins in saliva and play a role in the formation of dental pellicle and
influence initial microbial colonization on tooth surfaces.
2. Basic Proline-rich proteins,bind to hydroxyapatite of enamel crystals and inhibit the precipitation of calcium
and phosphate and maintain mineralization and demineralization of tooth surface by maintaining the calcium
and phosphorus level.BasicProline-rich proteins also play an important role in binding the cell wall of
microbes such as streptococci, thereby protecting the dental enamel from the microbial adherence and
neutralizing the acids produced by microbes. 17

Mucins 1e2 (Mucousglycoproteins)

Mucous glycol proteins (mucins) constitute a family with two members,-molecular-weight mucins (MG1)and low-
molecular-weight mucins (MG2).There is inverse relationship between Mucins 1 and 2 levels and the prevalence
of dental caries.

Anticaries property of Mucins

1. The mucins of saliva form a seromucosal cover that protects, lubricates, prevent the dehydration of oral cavity.
2. It also protects tissues against the proteolytic attacks of microorganisms.
3. It has antibacterial properties.
4. Mucins interact with several strains of streptococci and promote their agglutination, thereby accelerating the
clearance of bacteria from the oral cavity.
5. The mucins are present in acquired pellicle from tooth surfaces and protect teeth surface from
demineralization.17

Lactoferrin-
Lactoferrin (LF), also known as lacto transferrin (LTF), is a multifunctional protein. Lactoferrin has the
ability to bind and kill bacteria via direct interactions through the strongly basic N-terminal region of the
glycoprotein that consists of 47 amino acids

Anticaries property of Lactoferrin

1. It alter the permeability of the outer membrane of Gram-negative bacteria and releases bacterial lipo
polysaccharides LPS.31
2. Lactoferrin competes with various microorganisms in binding to free iron; this competition mechanism
has a bacteriostatic and bactericidal effect on various microorganisms that depend on this ion to survive. 17

Lysozyme
Lysozyme is an antimicrobial enzyme produced by animals that forms part of the innate immune system.

Lysozyme is found in high amounts in body fluids such as saliva, serum, tears and amniotic fluid, as well as in
low amounts in bile, urine and cerebrospinalfluid.

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Anticaries property of Lysozymes

1. Lysozyme promotes bacterial clearance through aggregation and adherence. 26
2. Lysozyme can activate bacterial autolysins and destroy the cell walls.
3. Lysozyme is an enzyme that destroys the bacterial cell wall of some bacteria. 17

Lactoperoxidase27:
Lactoperoxidase is a peroxidase enzyme secreted from mammary, salivary and other mucosal glands
including the lungs, bronchii and nose that functions as a natural and the first line of defense against bacteria
and viruses.

Anticaries property of Lactoperoxidase

It oxidizes thiocyanate (SCN -) in the presence of hydrogen peroxide which is formed by many oral organisms.
This antibacterial system is known to be inhibitory towards lactobacilli and some streptococci.

Cystatin S
Cystatins belongs to a heterogeneous family of proteins with a conserved consensus sequence in their active
site. Cystatins are cysteine proteinase inhibitors, antimicrobial and immune modulatory and are present in all
mucosal secretions.26

Anticaries property of Cystatin

1. Cystatins is responsible for the inhibition of cysteine proteases.
2. Cystatin S can be phosphorylated in five sites. The phosphorylated forms have an important function in
the regulation of calcium levels and in the pellicle formation.
3. The removal of the phosphate groups of cystatin reduces the affinity of the protein to hydroxyapatite. 17

Conclusion:-
Human saliva is a unique clear, slightly acidic (pH 6.0 to 7.0) biological fluid composed of 99% water and 1%
other compounds, such as a variety of electrolytes including sodium, potassium, calcium, magnesium,
bicarbonate and phosphates. Saliva also has immunoglobulins proteins, enzymes &mucins. On average,
individual salivation can range from 0.3to0.7ml of saliva per minute, producing a range of 1to1.5litres daily.
Saliva is easy to collect, to store, and can be obtained at low cost in sufficient quantities for analysis by a non-
invasive method. Thus it has the potential to be used in the early detection and diagnosis of various oral
diseases due to the abundant biomarkers present in saliva.

As a highly prevalent multi factorial disease, dental caries afflicts a large proportion of the world's population.
As teeth are constantly bathed in saliva, the constituents and properties of this oral fluid play an essential role
in the occurrence and progression of dental caries. Various inorganic (water and electrolytes) and organic
(proteins and peptides) components may protect teeth from dental caries. This occurs via several functions,
such as clearance of food debris and sugar, aggregation and elimination of microorganisms, buffering actions
to neutralize acid, maintaining super saturation with respect to tooth mineral, participation in formation of the
acquired pellicle and antimicrobial defense. Despite some controversial findings, the main body of the
literature supports an elevated caries prevalence and/or incidence among people with a pathologically low
saliva flow rate, compromised buffering capacity and early colonization or high titer of mutans streptococci in
saliva. 75.

These salivary biomarkers may be used for the prediction, diagnosis, prognosis and management of dental
caries, as well as for evaluating the outcome of therapeutic regimens. This was an attempt to provide an
overview of the current understanding of salivary biomarkers for dental caries. A few salivary tests, such as
salivary flow rate, buffering capacity and bacterial tests (for S. mutansand lactobacilli), have entered dental
clinical practice and can be used to assist the assessment of patients‟ caries risk. Various salivary parameters
should be combined with socio demographic, behavioral and clinical factors for a better estimate of patients‟
caries risk. Thus, advances in salivary analysis technology and further salivary research may lead to
breakthroughs (important discovery) in salivary biomarkers for dental caries.Although Saliva “ Lacks the
drama of blood, the sincerity of sweat and emotional appeal of tears” therefore saliva is still an overlooked
opportunity to reduce the burden and cost of diagnosis of Dental caries 26.

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