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Saliva testing or Salivaomics is a diagnostic technique that involves
laboratory A laboratory (; ; colloquially lab) is a facility that provides controlled conditions in which scientific or technological research, experiments, and measurement may be performed. Laboratory services are provided in a variety of settings: physici ...
analysis of saliva to identify markers of endocrine, immunologic, inflammatory, infectious, and other types of conditions. Saliva is a useful biological fluid for assaying steroid hormones such as cortisol, genetic material like
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
, proteins such as
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
s and antibodies, and a variety of other substances, including natural metabolites, including saliva nitrite, a biomarker for
nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its ...
status (see below for Cardiovascular Disease, Nitric Oxide: a salivary biomarker for cardio-protection). Saliva testing is used to screen for or diagnose numerous conditions and disease states, including Cushing's disease, anovulation,
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...
,
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
,
parasite Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted structurally to this way of lif ...
s, hypogonadism, and allergies. Salivary testing has even been used by the U.S. government to assess
circadian rhythm A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to ...
shifts in astronauts before flight and to evaluate hormonal profiles of soldiers undergoing military survival training. Proponents of saliva testing cite its ease of collection, safety, non-invasiveness, affordability, accuracy, and capacity to circumvent venipuncture as the primary advantages when compared to blood testing and other types of diagnostic testing. Additionally, since multiple samples can be readily obtained, saliva testing is particularly useful for performing chronobiological assessments that span hours, days, or weeks. Collecting whole saliva by passive drool has a myriad of advantages. Passive drool collection facilitates large sample size collection. Consequently, this allows the sample to be tested for more than one biomarker. It also gives the researcher the ability to freeze the left over specimen to be used at a later time. Additionally, it lessens the possibility of contamination by eliminating extra collection devices and the need to induce saliva flow. The clinical use of saliva testing occurred at least as early as 1836 in patients with bronchitis. Testing the acidity of saliva occurred at least as early as 1808. The testing of salivation by the use of mercury was performed at least as early as 1685. More recent studies have focused on detection of steroid hormones and antibodies in the saliva. Recent applications emphasize the development of increasingly sophisticated techniques to detect additional proteins, genetic material, and markers of nutritional status. According to Wong, scientists are now viewing saliva as "a valuable biofluid…with the potential to extract more data than is possible currently with other diagnostic methods."


Technique

Most saliva testing is performed using enzyme-linked immunosorbent assay (ELISA),
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
(PCR), high-resolution mass spectrometry (HRMS), or any number of newer technologies such as fiber-optic-based detection. All of these methods enable detection of specific molecules like cortisol, C-reactive protein (CRP), or secretory IgA. This type of testing typically involves collection of a small amount of saliva into a sterile tube followed by processing at a remote laboratory. Some methods of testing involve collecting saliva using an absorbent pad, applying a chemical solution, and monitoring for color change to indicate a positive or negative result. This method is commonly used as a point-of-care (POC) technique to screen for HIV. However, using absorbent pads and chemical solutions could very easily skew the results of immunoassays. Research by Dr. Douglas A. Granger and colleagues shows that outcomes for testosterone, DHEA, progesterone, and estradiol biomarkers are elevated when cotton-based collection materials are used as opposed to samples collected by other methods (i.e. passive drool). Researchers are currently examining the expanding role of saliva testing as part of routine dental or medical office examinations where saliva collection is simple to perform.


Physiologic basis

Humans have three major salivary glands: parotid, submandibular, and sublingual. These glands, along with additional
minor salivary glands The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of minor salivary glands. Salivary g ...
, secrete a rich mixture of biological chemicals, electrolytes, proteins, genetic material,
polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with ...
s, and other molecules. Most of these substances enter the salivary gland acinus and duct system from the surrounding capillaries via the intervening tissue fluid, although some substances are produced within the glands themselves. The level of each salivary component varies considerably depending on the health status of the individual and the presence of disease (oral or systemic). By measuring these components in the saliva, it is possible to screen for a variety of infections, allergies, hormonal disturbances, and neoplasms.


Clinical use

The following conditions are among those that can be detected through saliva testing (list not comprehensive): adrenal conditions (such as Cushing's disease/syndrome and Addison's disease), altered female hormone states (such as polycystic ovary syndrome
COS Cos, COS, CoS, coS or Cos. may refer to: Mathematics, science and technology * Carbonyl sulfide * Class of service (CoS or COS), a network header field defined by the IEEE 802.1p task group * Class of service (COS), a parameter in telephone sys ...
menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
, anovulation, and hormonal alterations in cycling women), altered male hormone states (such as hypogonadism/ andropause and
hyperestrogenic Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activ ...
states), metabolic disturbances (such as
insulin resistance Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood suga ...
,
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, and metabolic syndrome), benign and metastatic neoplasms (such as
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
,
pancreatic cancer Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts of the body. A number of types of panc ...
, and oral cancer), infectious conditions (such as HIV, viral hepatitis, amoebiasis, and
helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is th ...
infection), and allergic conditions (such as food allergy).


Uses in behavioral research

Saliva testing also has specific uses in clinical and experimental psychological settings. Due to its ability to provide insight into human behavior, emotions, and development, it has been used to investigate psychological phenomenon such as
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil Turmoil may refer to: * ''Turmoil'' (1984 video game), a 1984 video game released by Bug-Byte * ''Turmoil'' (2016 video game), a 2016 indie oil tycoon video ...
, depression, PTSD, and other behavioral disorders. Its primary purpose is to test cortisol and
alpha amylase α-Amylase is an enzyme (EC 3.2.1.1; systematic name 4-α-D-glucan glucanohydrolase) that hydrolyses α bonds of large, α-linked polysaccharides, such as starch and glycogen, yielding shorter chains thereof, dextrins, and maltose: :Endohydr ...
levels, which are indicative of stress levels. Salivary cortisol is a good stress index, with increased levels of cortisol correlating positively with increased levels of stress. Cortisol levels rise slowly over time and take a while to return to base level, indicating that cortisol is more associated with chronic stress levels. Alpha amylase, on the other hand, spikes quickly when confronted with a stressor and returns to baseline soon after the stress has passed, making salivary amylase measurement a powerful tool for psychological research studying acute stress responses. Samples are usually collected from participants by having them drool through a straw into a collection tube while experiencing a stimulus, with samples taken every few minutes to record the gradual change in stress hormone levels. Because the collection of saliva samples is non-invasive, it has the advantage of not introducing further stress on the participant that may otherwise distort results.