HARVARD GAZETTE ARCHIVES
Discovering who lives in your mouth:
Bacteria give clues to cancer and gum disease
By William J. Cromie
Eyes may be a window to the soul, but Donna Mager prefers looking into a mouth. She sees it as a mirror that reflects the body's health. It can reveal evidence for diabetes, measles, leukemia, syphilis, AIDS, bulimia, irritable bowel syndrome, heartburn, and other maladies. Obviously, oral cancer shows itself here, and she thinks it can be identified in its earliest stages by the communities of bacteria living in and on the mouth lining, tongue, and throat.
"It's amazing what you can see if you look carefully," says Mager, a fellow in oral medicine at the Forsyth Institute, an independent research institution in Boston. The view reveals hundreds of different kinds of bacteria, viruses, yeast, fungi, and other micro-organisms. Forsyth scientists, most of whom are on the faculty of the Harvard School of Dental Medicine, have found 615 different species of bacteria - and they're still counting.
It's a great place for micropests to dwell. Glistening white plateaus, dark crevices, and slimy surfaces boast steamy temperatures of 95 degrees Fahrenheit. The microbes bathe in a saliva-induced humidity of 100 percent, and eat a lavish diet of sugar and other carbohydrates. It's so lush and varied, Mager refers to it as a mini-jungle.
"In one mouth, the number of bacteria can easily exceed the number of people who live on Earth (more than 6 billion)," notes Sigmund Socransky, associate clinical professor of periodontology at Harvard. "These bugs don't colonize your mouth in a random way; rather, they form communities in a pattern that is dictated both by other bugs and by the environment. Bacteria affect their environment, and the environment affects them. Although they touch each other, the floor of the mouth is populated by different communities than the bottom of the tongue, and the top of the tongue hosts a biota unlike that on the roof of your mouth."
Years of detecting and identifying mouth tenants have revealed that those living in healthy mouths can be remarkably different from those living in diseased mouths. Some bacteria increase in number, while others decrease. By comparing communities of microbes in healthy people with those in the mouths of those with oral cancer, Mager has found a pattern that she expects will lead to the early diagnosis of oral cancers.
Something to smile about
However, the consensus on such a census is not yet firm enough for a trained dentist to tell if a person has oral cancer with one careful look. Most mouths, especially those of smokers and those who drink alcohol regularly, contain all kinds of benign abnormalities that confuse the picture. To be absolutely sure that the pattern she sees stems from oral cancer and not from noncancerous abnormalities, Mager must look into many more mouths.
To a base of 250 healthy people, she is adding oral cancer patients from Dana-Farber Cancer Institute, and Massachusetts General, and Brigham and Women's hospitals in Boston. Mager also hopes to recruit people with noncancerous abnormalities from patients at the Harvard School of Dental Medicine.
"It's slow work," she admits, and estimates that it will take another five to 10 years before she can come up with a reliable test for general use. "We have to be very sure," she adds. "I don't want to alarm people with a test that indicates they have cancer when they only have benign abnormalities."
An estimated 28,900 new cases of oral cancer will occur this year in the United States, including malignancies in the mouth, tongue, and throat. About 7,400 people die of such cancers each year. "Oral cancer is difficult to diagnose," Mager says. "If we can find it early with a sample of saliva or soft tissue lining the mouth, we should be able to reduce suffering and loss of life."
Succeeding at this would be a dream come true for Mager. She graduated from a Forsyth Institute program in dental hygiene at age 19. Mager wanted to go on to be a dentist, but marriage to a military man and raising children put that out of reach for the time being. Finally, after working 25 years as a hygienist and raising her kids to adulthood, she entered dental school at the University of Missouri at age 43. After graduation, Mager went on to earn a doctorate in medical sciences from the Harvard School of Dental Medicine this year. Then she joined Sigmund Socransky, who has been at the Forysth Institute since he completed dental school at the University of Toronto 45 years ago. He has spent this time closely investigating what lives in the human mouth, discovering new species and defining how their micro-communities change with disease.
Socransky believes he can use what he's learned to help diagnose many maladies in addition to oral cancer. He has associated a variety of gum diseases with shifts in populations of bacteria, viruses, yeast, and fungi. Taking it deeper, some of these mouth conditions are linked with problems like heart and blood vessel disease, strokes, pneumonia, and other respiratory ailments. This has led him to the conclusion that new evidence for diagnosing and treating a surprising assortment of diseases may be right under our noses.
Fighting bacteria with bacteria
Of course, all of the 600-plus types of bacteria living in your mouth don't cause disease. Some of them actively produce toxins that kill the pathogens. "Good bugs that kill bad bugs," Socransky calls them. "We'd love to replace the bad guys with good guys."
That's being tried, but it turns out to be difficult. Socransky and Jeff Hillman, now at the University of Florida, put billions of beneficial bacteria in their own mouths and swished them around. But the good guys could not establish residence. So they packed the bacteria into a paste, which they rubbed on their teeth and gums. That didn't work either. Then Socransky and Hillman saturated thick dental floss with bacteria, wrapped it around each tooth, and left it overnight.
"The best we could do was to get an occupancy of 21 days," Socransky admits. "And that's maximum. Most of the bacteria we tried to introduce disappeared within four to five days."
Hillman is trying to genetically engineer medicinal bacteria that will adhere to teeth and buffer the enamel-eating acid that produces decay. Experiments also are under way to make artificial saliva for people who don't make enough of this valuable anti-acid on their own, specifically those who undergo radiation for oral cancer or take medications that produce dry mouth.
Martin Taubman and Daniel Smith at Forsyth/Harvard Dental are having some success with a vaccine against cavities. They are ready to test it on children before they develop the stubbornly resistant communities of bacteria that plague people all of their lives.
Socransky feels confident that "efforts to survey the organisms that make their homes in human mouths will eventually yield the knowledge needed for accurate diagnoses of many diseases and for replacing the bad guys with the good."