The Biology of ... Saliva

Bye-bye, blood tests: Saliva may contain all a doctor needs to know about your body

By Kat McGowan|Monday, October 24, 2005

Babies drool. Old men dribble. Some people spit when they talk. The rest of us would rather not be reminded that saliva exists. Yet this humbling bodily fluid is powerful and critical to our existence. It heals wounds and disables pathogens. It is the perfect lubricant, permitting us to effortlessly eat, talk, kiss, and play a slide trombone. And now researchers think it could be as useful as blood in diagnosing disease: One day you’ll simply spit into a cup, and an analysis will show if you have problems ranging from heart disease to cancer.

“Most people treat saliva with disdain, as a nuisance more than anything else,” says Irwin Mandel, professor emeritus at the School of Dental and Oral Surgery at Columbia University. “They don’t realize how important it is. Those who have an absence of saliva are miserable.” Beyond the annoyance of dry mouth, people without saliva have a hard time keeping their teeth from rotting away.

Spit has buffers that keep the mouth’s pH slightly alkaline. Otherwise, the early stages of digestion that take place in the mouth would create an acid environment ideal for tooth-eating bacteria. Saliva also has a high concentration of calcium and phosphate ions, the main ingredients of teeth. Microscopic lesions in tooth enamel can be remineralized and thus protected by saliva—which is why dentists sometimes tell patients that they are “watching” a spot on a tooth.

But saliva’s bad reputation for hosting germs is somewhat justified. “The mouth is a perfect environment for growing bacteria, viruses, and fungi. It’s warm and dark, food goes in there several times a day, and there are lots of little nooks and crannies where food can get caught,” says dentist and oral microbiologist Donna Mager of the Forsyth Institute, a nonprofit group that focuses on oral and craniofacial research. Thanks to those pathogens, a punch in the mouth can be dangerous—for the aggressor. Busting a knuckle on someone else’s tooth can cause a serious infection.

Yet despite those bad actors, you will rarely get an infection by biting the inside of your cheek. That’s because saliva has a host of unique antibodies and antimicrobial compounds that can cause bacteria to clump together or to explode. Saliva can even disable HIV, which is why people are much less likely to get the virus through oral sex. Cheeks and gums tend to heal more quickly than skin, without scarring, thanks to proteins in saliva like vascular endothelial growth factor that promote the formation of blood vessels. This may also be why animals instinctively lick their wounds, says Daniel Malamud, a biochemist at New York University College of Dentistry.

Most of the bacteria in our mouths “are our friends,” says Mager. She estimates there are more than 700 species of commensal mouth bacteria, all living in distinct niches in about 33 square inches of the oral cavity, as dentists call it.

The mouth has many different habitats—the nonshedding hard surface of the teeth, the soft, papillate surface of the tongue, the smooth inside of the cheek—and “what grows on the tongue is very different from what grows on the palate or on the teeth,” says Mager. “No other place [in the body] has so many different types of environments.”

Mager has found that bacteria in mouths are not all the same and depend on where you happen to live. North Americans have different colonies from people in South America, who have different colonies from people in Sweden. Systemic diseases like diabetes also change the bacterial populations. To her surprise, Mager discovered that overweight women have different mouth bacteria from healthy normal-weight women.

In recent decades researchers have discovered that saliva contains a lot of information about the body. For example, the technique of measuring sex hormones in saliva is well established. Newer HIV tests can detect antibodies to the virus in saliva, and there are even salivary tests for illegal drug use.

Analyzing oral fluids may one day become common. Molecular biology and microfluidics have spawned powerful techniques for isolating and manipulating small amounts of biological materials, making salivary diagnostics possible. As a diagnostic fluid, saliva has plenty of benefits over blood. For starters, getting a sample doesn’t require a trained technician, and there are no hypodermic needles involved.

With that in mind, the National Institute of Dental and Craniofacial Research is funding seven teams of researchers to build salivary diagnostic devices. The projects bring together biologists, dentists, and bioengineers and span a range of technologies, from an artificial nose that can sniff out infectious particles to a genetic test that can identify fragments of RNA in saliva that have been linked to cancers. Microfluidics, the science of moving nanoliter-size drops of liquid through channels built on the scale of a cross section of a human hair, make it possible to automate the process of separating out biomarkers, analyzing and amplifying them, and then registering their presence. “Conceptually, we’re really not that far away,” says Lawrence Tabak, director of the institute. “It’s been catalyzed by the extraordinary efforts of bioengineers, who can take what used to be a whole room of fancy equipment and shrink it to the size of a business card—it’s amazing.”

Malamud’s group, for instance, is using miniaturized genetic analysis and immunology techniques, combined with phosphorescence-based signaling, to build a device that may quickly identify common childhood infections. Almost all childhood respiratory disease is caused by one of seven viral or bacterial culprits, but when a sick kid shows up at a doctor’s office, there’s no easy way to tell which is to blame. Malamud’s microfluidic machine uses four microscopic channels to simultaneously scan a sample: The first looks for human antibodies to the infectious agent, the second for an antigen on the surface of the pathogen, and the third and fourth amplify viral RNA or bacterial DNA. The sample then flows onto a detector sheet, where any positive “hits” appear as phosphorescent signals.

The catch with saliva is that in many cases the biology of how biomarkers appear in saliva, and what they mean, has not been fully explained. “The ratio of the oral level to blood level may be perfect, as in the case of alcohol,” Malamud says. “Or it may be meaningless, as is the case with glucose. You can measure glucose in an oral sample, but it has no correlation to the level in the blood.” Focusing on conditions like gum disease or oral cancer reduces those hurdles. One team at UCLA has had success in detecting signs of oral cancer by analyzing the RNA found in saliva.

Within a few years, these seven groups of researchers hope to build fully automated, tabletop-size diagnostic machines that can be stationed in a clinic, a dentist’s office, or even at home. At that scale, analysis can happen more quickly and cheaply. With fewer jabs in the arm, no more throat scrapings, and fewer urine samples, saliva could end up a patient’s hero.

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