The Path of Least Resistance

How Bacteria Sneak Into Your Blood Through Your Mouth

The inside of the human body is a bacteria-free zone. Bacteria are certainly within you, but they exist only in areas that have a direct channel to the outside world, such as the mouth, intestines and the surface of the skin. These areas are well protected by a layer of cells (epithilial cells) which form a protective barrier to keep away the nasties of the outside world. That’s why there are healthy stomach bacteria, but no healthy liver bacteria. From a certain point of view your lungs and digestive tract still are the outside world, which is why bacteria can get in and live there, sometimes perfectly happily without causing any trouble at all.

Major problems start to happen, however, once bacteria get through that epithelial barrier and into the tissues of your body. Which is why the first bacteria of the new year is the oral bacteria Fusobacterium nucleatum, which has a trick to open up little doors in blood vessels. These aren’t massive holes, not big enough to cause bleeding but large enough to let it and other bacteria into the bloodstream.

The bacteria in all their blobby glory! These are actually the related Fusobacterium novum. Image taken from the CDC Public Health Image Library (link below).

This is a big issue, because once the bacteria get into the blood-stream they can travel around anywhere within the body. It’s not  just the blood-vessels in the mouth that the F. nucleatum can get into, it can also bypass a lot of other cellular barriers such as the blood-brain barrier that keeps bacteria out of your brain, and the placental barrier that guards the passage of substances between a pregnant mother and the foetus.

The bacteria works by releasing a chemical which is picked up by the cells that make up blood vessels (endothelial cells) and causes the cells to become more permeable. More technically the bacterial chemical (a FadA adhesin) binds to a protein on the cells (vascular endothelial cadherin) that helps to keep the endothelial cells joined together and causes it to migrate away from the cell-cell junction. This opens the junctions up slightly and makes the whole vessel more permeable.

Endothelial cells that form a lining around the blood-vessels. Cell-cell junction in blue and nucleus in red. Pic (c) me.

FadA (the bacterial chemical) is an interesting little molecule, and while it’s highly conserved in F. nucleatum and related oral bacterial species, it has been lost in many closely related species which do not populate the human mouth. This is a protein with one specific purpose – to open blood vessels – and where that function is not needed the bacteria has no need for the protein. When it’s first made by the cell it exists in a form called pre-FabA which anchors to the bacterial membrane with the soluble part (the actual FabA) on the outside of the bacteria ready to be deployed.

To test whether the FabA and the cell cadherin could bind, the researchers carried out a whole range of different binding tests (more information in the  reference below). First, they did a yeast-two-hybrid screen, a sort of sciency quick and dirty method to see if two proteins can bind each other. Then they took both proteins out of the cell to see if they could bind separately, by sticking one protein to a column and seeing if it could ‘catch’ the other as it was washed through. Finally they put both proteins back in the cell with coloured markers attached to see if the coloured markers appeared in the same places. All of these results, along with the actual structures of the two proteins, suggest very strongly that they bind.

One of the most interesting tests they did was to see whether the F. nucleatum was just opening the floodgates for itself, or whether other bacteria were sneaking in at the same time. They did this by making little wells with endothelial tissue between them. Sure enough, those cultures containing E. coli along with F. nucleatum showed that both bacteria could travel through the endothelium together, whereas in cultures containing only E. coli the bacteria remained on one side of the membrane.

If Your Teeth Could Talk...

The Mouth Offers Clues to Disorders and Disease;

Dentists Could Play Larger Role in Patient Care

The eyes may be the window to the soul, but the mouth provides an even better view of the body as a whole.

Some of the earliest signs of diabetes, cancer, pregnancy, immune disorders, hormone imbalances and drug issues show up in the gums, teeth and tongue—sometimes long before a patient knows anything is wrong.

There's also growing evidence that oral health problems, particularly gum disease, can harm a patient's general health as well, raising the risk of diabetes, heart disease, stroke, pneumonia and pregnancy complications.

"We have lots of data showing a direct correlation between inflammation in the mouth and inflammation in the body," says Anthony Iacopino, director of the International Centre for Oral-Systemic Health, which opened at the University of Manitoba Faculty of Dentistry in Canada in 2008. Recent studies also show that treating gum disease improves circulation, reduces inflammation and can even reduce the need for insulin in people with diabetes.

Such findings are fueling a push for dentists to play a greater role in patients' overall health. Some 20 million Americans—including 6% of children and 9% of adults—saw a dentist but not a doctor in 2008, according to a study in the American Journal of Public Health this month.

"It's an opportunity to tell a patient, 'You know, I'm concerned. I think you really need to see a primary care provider,' so you are moving in the direction of better health," says the study's lead researcher Shiela Strauss, co-director of statistics and data management for New York University's Colleges of Nursing and Dentistry.

George Kivowitz, a restorative dentist with offices in Manhattan and Newtown, Pa., says he has spotted seven cases of cancer in 32 years of practice, as well as cases of bulimia, due to the telltale erosion of enamel on the back of the upper front teeth, and methamphetamine addiction. "We call it 'meth mouth,' " he says. "The outer surface of teeth just rot in a way that's like nothing else."

Some of the most distinctive problems come from uncontrolled diabetes, Dr. Kivowitz adds. "The gum tissue has a glistening, shiny look where it meets the teeth. It bleeds easily and pulls away from the bone—and it's all throughout the mouth."

An estimated six million Americans have diabetes but don't know it—and several studies suggest that dentists could help alert them. A 2009 study from New York University found that 93% of people who have periodontal disease are at risk for diabetes, according to the criteria established by American Diabetes Association.

It's not just that the same lifestyle habits contribute to both gum disease and high blood sugar; the two conditions exacerbate each other, experts say. Inflammation from infected gums makes it more difficult for people with diabetes to control their blood-sugar level, and high blood sugar accelerates tooth decay and gum disease, creating more inflammation.

Dr. Marcus notes that about 50% of periodontal disease is genetic—and even young patients can have significant bone loss if they have an unusually high immune response to a small number of bacteria. Giving such patients a low dose of doxycycline daily can help modify the immune response. "It doesn't really control the bacteria, but it helps reduce the body's reaction," he says.Diabetes also complicates dental-implant surgery, because it interferes with blood vessel formation and bone growth. "When you put a dental implant in, you rely on the healing process to cement it to the jaw, so you get a higher failure rate with diabetes," says Ed Marcus, a periodontist in Yardley, Pa., who teaches at the University of Pennsylvania and Temple University dental schools.

There's also growing evidence that the link between periodontal disease and cardiovascular problems isn't a coincidence either. Inflammation in the gums raises C-reactive protein, thought to be a culprit in heart disease.

"They've found oral bacteria in the plaques that block arteries. It's moved from a casual relationship to a risk factor," says Mark Wolff, chairman of the Department of Cariology and Comprehensive Care at NYU College of Dentistry.

Bacteria from the mouth can travel through the bloodstream and cause problems elsewhere, which is why people contemplating elective surgery are advised to have any needed dental work performed first.

The American Heart Association no longer recommends that people with mitral valve prolapse (in which heart values close abnormally between beats) routinely take antibiotics before dental procedures, since it's now believed that oral bacteria enter the bloodstream all the time, from routine washing, brushing and chewing food.

But the American Heart Association, the American Medical Association and the American Orthopedic Association all urge people who have had a full joint replacement to take an antibiotic one hour before any dental visit for the rest of their lives to reduce the risk of post-surgical infections. "I have my guidelines taped to the door in my hygienists' room," Dr. Kivowitz says.

Dentists say they also need to stay up to date with all medications, supplements and over-the-counter drugs their patients are taking. Blood thinners can create excess bleeding in the mouth. Bisphosphonates, often prescribed for osteoporosis, can severely weaken jaw bones. Both should be stopped temporarily before oral surgery.

Antihypertensive drugs, calcium-channel blockers and some anti-inflammatory drugs can cause painful ulcerations of the gums. Many medications, from antidepressants to chemotherapy drugs, cause dry mouth, which can cause cavities to skyrocket, since saliva typically acts as a protective coating for teeth. Additional fluoride treatments can help.

Some proactive dentists have glucose monitors for another check on blood-sugar levels if they suspect diabetes. Some also take patients' blood pressure and hold off on invasive procedures if it's extremely high.

The Centers for Disease Control and Prevention recommends that dentists offer HIV testing, because some of the first symptoms appear in the mouth, including fungal infections and lesions. Dentists can do the HIV test with a simple mouth swab and get results in 20 minutes.

Breaking the bad news is often more difficult. "I went into oral surgery because I didn't think I would have to deliver that kind of news to patients," says Clifford Salm, an oral and maxillofacial surgeon in Manhattan who has found leukemia, lymphoma, AIDS and metastatic breast cancer after performing biopsies on suspicious spots. "It can be a difficult conversation," he says, "but most patients are very grateful."

Don't Be Fooled by White, Shiny Teeth
A gleaming, white smile is a sign of a healthy mouth, right? Not necessarily.  "Whiteness and the health of your teeth are totally unrelated," says Mark Wolff, an associate dean at New York University College of Dentistry.

In fact, many dentists worry that people who whiten their teeth may have a false sense of complacency, since their teeth can still be harboring tooth decay and serious gum disease.

Even people who have no cavities can still have inflamed and infected gums. It could be that their saliva is particularly protective of their tooth enamel, while their brushing and flossing habits, needed to keep gum tissues healthy, could be lax.

"I get these patients in their mid-30s who don't have cavities, so they haven't been to a dentist in 10 years. But they have full-blown periodontal disease," says George Kivowitz, a restorative dentist in Manhattan. "They are losing all the supporting structure, and I have to tell them that these gorgeous teeth will fall out of your head if we don't turn this around."

Using whitening products more often than recommended can erode some of the enamel and cause teeth to appear translucent. But whether that actually harms teeth is controversial. "No one has really shown that it's damaging, but no one knows the long-term results," says Dr. Marcus, the periodontist in Yardley, Pa.

The Mouth-Body Connection: Garbage In=Garbage Out

Discover why good dental health depends on more than brushing and flossing, and why a clean, happy mouth gives your whole body something to smile about.

By Bonnie Blodgett

Let's face it. Most of us take our teeth for granted. Sure, we brush and floss (well, some of the time). And we know, of course, that teeth are essential for chewing our food and for maintaining a beautiful smile. But when we get a cavity – or even when we get diagnosed with gum disease that might culminate in root canals or tooth loss – we seldom think of these problems as posing permanent risks to our health and vitality.

We simply don't place the same importance on our dental health as we do on, say, the health of our vital organs. After all, the mouth is the domain of the dentist; the body, the domain of the doctor.

But that perspective is changing. Recent research provides convincing evidence that oral health and overall health are inextricably linked – that what's good for our mouth is also good for the rest of the body we work so hard to keep fit and healthy. Dentists increasingly screen for systemic diseases, which involve many organs or the whole body, through tongue assessments, saliva tests, blood pressure checks, and simple observation of the teeth and gums. As well they should: More than 90 percent of systemic diseases have oral symptoms such as lesions, according to the Academy of General Dentistry. Dentists are also checking for signs of inflammation that could affect heart health as we age. When they see trouble, they make referrals to physicians.

To emphasize the connection between oral health and overall health, Vincent J. Iacono, DMD and former president of the American Academy of Periodontology, offers the not-so-appealing metaphor of the mouth as a garbage dump on the edge of a river: "You wouldn't be surprised if the lake downstream ended up polluted with the garbage from the dump. A patient's bloodstream acts very much like the river in this analogy, in that it carries the bacteria from the periodontal plaques, possibly 'polluting' the arteries of the heart with periodontal bacteria, causing inflammation of the arteries, which may lead to a heart attack. This potential effect of periodontal bacteria further supports the need for periodic deep cleanings to enhance overall health and well-being."

This same effect has also convinced the American Heart Association (AHA) that dentists are very much on the front lines of healthcare. In addition to helping us keep our teeth firmly planted in our mouths as we age, oral-health experts are also destined to play a more important role in helping us maintain our vitality and overall quality of life.

A New Approach to Dental Health
This link between oral and overall health, now becoming common in conventional dentistry, has for years been a key tenet of what's known as holistic dentistry, which takes an integrated approach to dental care. Holistic dentists advocate for optimal nutrition. They take a minimally invasive approach to resolving dental problems. Some even evaluate a patient's skeletal structure and, of greatest controversy, often shun the use of fillings that contain mercury and call for replacing those amalgams.

Holistic dentists consider conventional dentists too quick to remove troublesome teeth, perform root canals, and insert "unnatural" substances and appliances into the mouth, arguing that these toxic substances create unhealthy imbalances in the mouth's natural ecosystem. But there are signs that the members of the Holistic Dental Association and the American Dental Association (ADA) may be inching closer together, at least philosophically.

Conventional dentists like P. Piero, DDS, of Holland, Mich., an ADA member in good standing, have some doubts about many of holistic dentistry's claims and methods. But Piero is pushing his colleagues further in the direction of what many in the profession are calling a "whole-person" approach to dentistry. Piero, who has spent two decades developing his own oral-care system (www.dentalairforce.com), represents a new breed of dental practitioner. He considers himself a teacher and passes along what he learns about oral health and hygiene to his patients. He isn't shy about discussing the difference between good and bad bacteria, their role in building plaque, and what happens when the bad guys get loose in the bloodstream. A visit to Piero may include a conversation about changes in diet and lifestyle – changes, he emphasizes, that could prevent not only tooth decay but also tooth loss. He knows that the longer his patients keep their teeth, the longer they're likely to live.

Healthy Mouth, Healthy Body
Good oral health calls for more than just brushing and flossing. It requires eating nutritious foods, exercising, avoiding cigarettes and alcohol, and controlling blood pressure. It may also mean looking to your dentist as a resource for more than cleanings and fillings. After all, troubles in the mouth not only predict disease, they can also exacerbate and even cause it.

John Laughlin III, DDS, of River Falls, Wis., has been practicing holistic dentistry for years. Many patients come to him when nothing else has eased their chronic pain or fatigue. Laughlin recalls one woman who came to him because she developed such severe flulike symptoms following a root canal that she "thought she was dying." She'd consulted several doctors who could find no cause for her symptoms.

Laughlin, suspecting an infection below the crown capping the root canal, referred her to an oral surgeon to have the tooth removed. The oral surgeon refused because, as Laughlin puts it, "he could see nothing wrong with the tooth." Six weeks and three doctors later, the woman finally signed papers absolving her surgeon of any responsibility for the outcome. He then removed the tooth – and found that the dead nerve remnant beneath it was not only infected but that the infection had spread to the bone, which was badly eroded.

More surgery was required to fill the large hole with bone taken from her inner cheek. The woman's symptoms immediately disappeared. She credits Laughlin with saving her life.

An equally convincing and more far-reaching example of the mouth-body health connection is evidenced by the well-established link between periodontal disease (infected gum tissue that can lead to tooth loss) and cardiovascular illness. Such disease is now considered as reliable a predictor of cardiovascular disease as smoking, diabetes, hypertension, high cholesterol and elevated serum triglycerides. A 2004 AHA study found that pericoronitis (infected wisdom teeth) heads the list of dental risk factors for heart disease. Others, in order of importance, are gingivitis, root remnants, cavities and missing teeth.

Periodontal disease has also long been associated with diabetes; now it's being linked to other chronic illnesses involving not just the heart but also the lungs and the brain, and to low-birth-weight babies and preeclampsia (a condition characterized by high blood pressure and the presence of protein in the urine). It is also known to be more prevalent in postmenopausal women, probably because of lower estrogen levels, which also cause bone loss and, not incidentally, heart disease.

How all these problems intersect remains somewhat mysterious. Consider tooth loss: Like other oral health problems, it involves a vicious cycle. An older person who has lost teeth and can't chew properly doesn't get all the nutrition available in food, which exacerbates the underlying problem that caused his or her teeth to have a precarious grip in the first place. In other words, the gum disease itself may have a nutritional basis (too many doughnuts and soft drinks, perhaps), which in turn caused systemic problems such as poor bone health or a chronic disease. Healthcare providers do know that tooth loss is a predictor of longevity (the longer we keep our teeth, the longer we live) and that losing teeth nearly doubles a person's heart-attack risk.

Inflammation and Cardiac Illness
Need more convincing about the mouth-body connection? Consider the death of a middle-aged man who'd had a defective heart valve replaced and seemed to be recovering well: He was told to take antibiotics before dental visits to prevent infection from bacteria that can escape from the mouth into the bloodstream during cleaning. Apparently the antibiotics weren't enough to prevent a massive infection, which led to a fatal heart attack.

The fact that inflammation – often a result of infection – causes strokes and heart attacks has been widely accepted and is now being studied in depth by the AHA. Nowadays, it's not unusual during a routine physical to be given a test for C-reactive protein, a marker for systemic inflammation, especially if you have other risk factors for heart disease. Bad teeth, poor oral hygiene and diet are usually implicated when inflammation is detected.

Saliva is our first line of defense against the "bad" bacteria that cause plaque to form on our teeth. Plaque buildup may cause gingivitis, which can lead to periodontitis and, if left unchecked, to something called acute necrotizing ulcerative gingivitis, or trench mouth. Bacteria from those conditions can enter the bloodstream after routine dental cleanings, or even after flossing and brushing at home. Bad bacteria can also make its way into the bloodstream when saliva flow is reduced because of antibiotics or medications, such as antidepressants, disrupting the normal bacterial balance of the mouth.

Bacteria that manage to slip into the bloodstream (called bacteremia) could cause an infection elsewhere, especially if a body's immune system has been weakened by a disease like AIDS or by cancer treatments. And if those bad bacteria find their way to the lining of diseased heart valves, the result can be infective endocarditis. That's the condition that took the life of that middle-aged man who thought he was on the road to cardiac health, but died after a routine dental cleaning.

The Case for Good Hygiene
In his practice, Piero addresses systemic problems with patients even as he is filling their cavities or helping them decide whether to straighten their crooked teeth. He considers anything unnatural in the mouth dangerous (whether a crown, an implant or a cosmetic veneer), but not because of the fear of mercury toxicity often cited by holistic dentists. Rather, he says, such things interfere with what he thinks is the most important issue in dentistry: the battle against bad bacteria.

"The mouth is a war zone," Piero says, referencing the more than 500 species of bacteria that inhabit it. "Bad bacteria are usually anaerobic – they live in the absence of air." Their excrement turns into plaque, which is actually a multilayered biofilm and very difficult to remove once it's got a foothold, and especially dangerous if its presence has created periodontal inflammations known as pockets. This process causes illness in other parts of the body not just by allowing bad bacteria into the bloodstream but also by causing the body to fight back with enzymes called cytokines that trigger a systemic inflammatory response. He believes this cycle is the primary link between oral and whole-body health.

"Hygiene is everything," says Piero, who recommends patients visit him four times a year for intensive cleanings, rather than the standard twice-yearly visits. "A 16-year-old kid can have perfect teeth, but his beautiful smile won't last long without good dental habits. It's like letting your new Ferrari sit out in the rain. I'm looking at the long term. Our kids are going to live to be 100. Their teeth have to last that long, too."

Piero points out that bacteria can be spread through any sort of contact. "Yes, periodontal disease is hereditary, but it is also an infectious disease. Kissing, eating – many activities bring new kinds of super-smart bacteria into the mouth. They are highly adaptive: They can change quickly to new conditions in order to survive."

Given the potential impact oral conditions can have on our total health, says Piero, it would be wise for us to show the same respect for our teeth that we would to other parts of the body. "The area of our exposed gum tissue equals that of our forearm, about 9 square inches," he points out. "What would we do if suddenly our forearm was inflamed? We'd run to the doctor. But periodontal disease is painless. Hidden." And so we ignore it.

Dentistry for Life
Jessica Saepoff, DDS, belongs to the ADA and five other major dental organizations. Like Piero, she has developed her own interpretation of holistic dentistry. Her practice, Natural Dental Health Associates, in Issaquah, Wash., specializes in alternative methods, which she considers not so much alternative as simply the most advanced. She routinely communicates with her patients' other holistic health practitioners so they can work together toward comprehensive health goals.

For Saepoff, dental care always comes down to personal choice. "I tend to attract patients who are opposed to taking even small theoretical risks, whether it's eating pesticides in their food or having mercury in their mouths," she says. "I understand that drilling is sometimes necessary, but the goal of my practice is to preserve natural tooth structure."

Whether you take the holistic path to oral health or the conventional approach, one thing is certain: The way you think about your teeth may change dramatically in coming years, as new studies shed more light on the myriad ways in which a healthy mouth is essential to overall health and vitality, and a key factor in longevity. With your doctor and your dentist by your side, you'll be able to keep your smile beautiful, and to keep flashing that great grin for years to come.

Bonnie Blodgett is a writer and editor in St. Paul, Minn. She publishes a quarterly for gardeners, The Garden Letter, and is working on a book about smell.

Oral Bacteria & Pneumonia - Is There A Link?

Oral bacteria linked with pneumonia risk

By Rabia Mughal, Contributing Editor

November 18, 2011 -- Oral microbiota could play a role in identifying patients at risk for healthcare-associated pneumonia, according to a study presented October 22 at the Infectious Diseases Society of America annual meeting in Boston.

"The bodies of healthy individuals are cohabited by an incredible number of bacteria, where bacterial cells outnumber human cells 10 to 1," said study author Samit Joshi, DO, MPH, from the department of internal medicine at the Yale University School of Medicine, in an interview with DrBicuspid.com.

Scientists are now learning how different communities of bacteria reside in different parts of the body and how they can directly or indirectly influence states of health or disease, including pneumonia.

“Changes in oral bacteria play a role in the risk for developing pneumonia.”
— Samit Joshi, DO, MPH

Dr. Joshi and his colleagues wanted to determine if an association existed between the oral microbial profile and subsequent development of pneumonia.

They used advanced DNA sequencing to show that the types of bacterial communities that normally reside in adults' mouths change substantially as their risk for developing pneumonia increases.

While presenting his study at the meeting, Dr. Joshi reported that there was a distinct divergence between the oral bacteria of mechanically ventilated intensive care unit (ICU) patients who developed pneumonia and those who did not.

"In the case of hospitalized adults on mechanical ventilators, the change in bacteria preceded the development of pneumonia," Dr. Joshi said. "This suggests that changes in oral bacteria play a role in the risk for developing pneumonia."

Streptococcaceae dominant

Healthcare-associated pneumonia is a growing public health problem, but strategies to identify high-risk patients remain problematic, according to Joshi and his colleagues. While impaired oral hygiene is a known modifiable risk factor, the precise alterations in oral microbiota are unknown, they added.

The researchers looked at 37 subjects who were prospectively followed for a one-month period. The subjects included healthy community-dwelling adults (19, average age 60) and those at risk for healthcare-associated pneumonia: nursing home residents (10, average age 86) and mechanically ventilated ICU patients (8, average age 51).

The authors used a technique called 16S rRNA gene pyrosequencing to compare the oral microbial profiles of the study participants.

They found that the dominant bacteria in the mouth were Streptococcaceae but that the proportion differed across the three clinical settings, with community dwellers averaging 65%, nursing home residents at 43%, and the mechanically ventilated ICU patients at 33% (p = 0.02 for ventilator patients versus community dwellers).

While the ICU subjects who subsequently developed pneumonia had a significantly smaller average proportion of oral Streptococcaceae (7%) at baseline compared with the ICU subjects who did not develop pneumonia (49%, p = 0.02), the proportions of three other groups -- the Enterococcaceae, the > Micrococcaceae, and the Mycoplasmataceae -- rose sharply in this group.

Also, the bacterial community composition among ICU subjects who developed pneumonia was significantly different from the ICU subjects who did not develop pneumonia.

"Oral microbial profiles differ in community-dwelling adults compared to those in healthcare settings at high risk for pneumonia," the authors concluded. "Mechanically ventilated ICU subjects who subsequently developed pneumonia had a distinct divergence of their oral microbial profiles compared to ICU subjects who did not develop pneumonia."

Pyrosequencing of oral microbiota could be helpful in identifying patients at high risk of healthcare-associated pneumonia, they added.

However, it will still be a number of years filled with additional intensive research before these preliminary findings can be used to improve prevention and clinical care for patients at high risk of developing pneumonia, he added.  "By discovering how microbial communities change prior to the development of pneumonia, physicians and scientists could develop new techniques to identify patients at risk for pneumonia and discover new ways to prevent pneumonia in the future," Dr. Joshi concluded.