Each year, cardiovascular disease kills more Americans than cancer. And while most people are aware that lifestyle choices such as eating right, getting enough exercise and quitting smoking can help prevent cardiovascular disease, they may not know that by just brushing and flossing their teeth each day, they might also be avoiding this potentially lethal condition.

An article published a recent Journal of Periodontology (JOP), the official publication of the American Academy of Periodontology (AAP), suggests that periodontal patients whose bodies show evidence of a reaction to the bacteria associated with periodontitis may have an increased risk of developing cardiovascular disease.

"Although there have been many studies associating gum disease with heart disease, what we have not known is exactly why this happens and under what circumstances," said JOP editor Kenneth Kornman, DDS, PhD. "The findings of this new analysis of previously published studies suggest that the long-term effect of chronic periodontitis, such as extended bacterial exposure, may be what ultimately leads to cardiovascular disease."

Researchers at Howard University identified 11 studies that had previously examined clinically-diagnosed periodontal disease and cardiovascular disease. The team then analyzed the participants' level of systemic bacterial exposure, specifically looking for the presence of the bacteria associated with periodontal disease, as well as measuring various biological indicators of bacterial exposure. They found that individuals with periodontal disease whose biomarkers showed increased bacterial exposure were more likely to develop coronary heart disease or atherogenesis (plaque formation in the arteries).

"While more research is needed to better understand the connection between periodontal disease and cardiovascular disease, this study suggests the importance of taking of your teeth and gums and how that can help you take care of your heart," said Susan Karabin, DDS, President of the AAP. "With the number of people with heart disease continuing to increase, it is important to understand that simple activities like brushing and flossing twice a day, and regular visits to your dental professional can help lower your risk of other health conditions."

Scientists studying young adults in New Zealand have revealed that smoking cannabis (marijuana), independent of tobacco, is a potential risk factor for gum disease.

The study is published in the 6th February issue of the Journal of the American Medical Association (JAMA) and was the work of researchers based at the Dunedin School of Medicine in New Zealand; King's College London, England; Duke University, Durham, North Carolina, USA; and the University of North Carolina, Chapel Hill, also in the USA.

Inflammation associated with periodontal disease (disease of the bone, gum or ligaments that anchor and support the teeth) can extend deep into dental tissue, weakening its supportive structure and resulting in loose teeth and eventually tooth loss as well.

Periodontal disease is one of the most chronic diseases in adults, wrote the researchers.

Scientists already knew that smoking tobacco was significantly linked to increased risk of periodontal disease, but there was no information on how cannabis smoking, with our without tobacco smoking, may or may not have the same connections.

In this study Dr Murray Thomson, of the Dunedin School of Medicine, and colleagues, put together a prospective cohort representative of the general population and examined cannabis use at ages 18, 21, 26 and 32 years.

They also did dental checks at ages 26 and 32 years, for which the most recent were completed in June 2005. The 1,015 participants were born in Dunedin, New Zealand, between 1972 and 1973. From these 903 (89 per cent) completed records were obtained for the duration of the study and used in the analysis.

The main outcome measure the researchers looked for was periodontal disease status at age 32 (including changes that had occurred since the previous exam at age 26). This was assessed from a measure known as periodontal CAL (combined attachment loss) which indicates how well or poorly the periodontal tissue is holding onto its teeth.

They defined cannabis exposure in three categories: no exposure, some exposure, and high exposure. No exposure was defined as not using cannabis during the period assessed, some exposure was defined as using cannabis on average between 1 and 40 times, and high exposure was 41 or more times.

The analysis showed that:

* 293, or 32.3 percent of participants fell into the no exposure group.

* 428, or 47.4 per cent of the participants had had some exposure.

* And 182, or 20.2 per cent of the participants had had high exposure.

* At the age of 32 years, 29.3 per cent (265) of the participants had one or more sites with 4 mm or greater amount of CAL, and 12.3 per cent (111) had one or more sites with 5 mm or more CAL.

* New CAL that appeared between the ages of 26 and 32 went up in line with cannabis exposure (ie higher cannabis exposure linked to worse gum disease).

* The no cannabis exposure group had an average of 6.5 per cent of new CAL.

* For the some exposure group this figure was 11.2 per cent.

* For the high exposure group it was 23.6 per cent.

* After controlling for tobacco smoking (using pack-years), gender, irregular attendance at the dentist, and amount of dental plaque, the high cannabis exposure group had a 60 per cent increased risk of having one or more CAL sites of 4 mm or more, a 3.1 times greater risk of one or more 5 mm CAL sites, and a 2.2 times greater risk of new CAL.

* Tobacco smoking was strongly linked to periodontal disease, but there was no interaction between cannabis use and tobacco smoking in predicting the condition's occurrence.

The researchers concluded that:

"Cannabis smoking may be a risk factor for periodontal disease that is independent of the use of tobacco."

They suggested that:

"The study's demonstration of a strong association between cannabis use and periodontitis experience by age 32 years indicates that long-term smoking of cannabis is detrimental to the periodontal tissues and that public health measures to reduce the prevalence of cannabis smoking may have periodontal benefits for the population."

Shoud these findings be comfirmed by other studies, they suggested that health authorities and practitioners start raising awareness that cannabis use damages teeth and gums.

Bacteria that eat sugar and release cavity-causing acid onto teeth may soon be made dramatically more vulnerable to their own acid. Researchers have identified key genes and proteins that, if interfered with, can take away the ability of a key bacterial species to thrive as its acidic waste builds up in the mouth.

The ability of Streptococcus mutans (S. mutans) to survive in acid is one reason that the species is the main driver of tooth decay worldwide. Past research has shown that this ability has several components including a bacterial enzyme called fatty acid biosynthase M (FabM), which when shut down, makes S. mutans almost precisely 10,000 times more vulnerable to acid damage.

In addition, early work suggests that FabM or one of its relatives may also help all Streptococci (strep) and Staphylococci (staph) infections to resist the human body's defenses, which include immune cells that subject bacteria to acid. Between them, "strep" and "staph" bacteria are responsible for meningitis, pneumonia, sepsis, methicillin-resistant staph aureus, the "flesh-eating" infection (fasciitis), as well as infections on heart valves and around stents.

While FabM represents a major target for the design of new drugs, the focus of the next round of work is to identify and rank every one of the 2,000 known S. mutans genes that contributes to its "fitness" (ability to survive, out-compete other strains and cause disease). A research team at the University of Rochester Medical Center today announced that it has received a $3.6 million fitness profiling grant from the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health (NIH). Grant-funded projects will seek to create a catalogue of proteins that, along with FabM, can serve as targets for a multi-pronged attack on bacteria that tend to evolve around single-thrust treatments.

"Our first goal is to force the major bacterium behind tooth decay to destroy itself with its own acid as soon as it eats sugar," said Robert G. Quivey, Ph.D., professor of Microbiology & Immunology at the University of Rochester Medical Center and principal investigator for the grant. "After that, this line of work could help lead to new anti-bacterial combination therapies for many infections that have become resistant to antibiotics."

Study Details

In 2002, Charles O. Rock, Ph.D., a faculty member within the Department of Infectious Diseases at St. Jude Children's Research Hospital, published his research describing the existence of the FabM enzyme. Rock, a consultant on Quivey's grant application, also established the role that the FabM gene plays in the construction of compounds called fatty acids in the membranes of strep bacteria, a barrier they present to surrounding world. Applying the FabM line of work to oral disease for the first time, Quivey and colleagues about two years later published research that FabM enzymes were behind dramatic changes seen, in response to increasing acidity, in the fatty acids that compose the S. mutans membrane.

S. mutans produces lactic acid as a waste product of fermentation, the process by which some ancient lifeforms convert sugar into energy for life without using oxygen. After a great many generations of exposure to its own acid waste, the membranes for this species have become "acid durable." Quivey's team has shown that FabM contributes to this durability by making carbon chains, the main functional feature of S. mutans membrane fatty acids, grow longer. In fact, as many as 60 percent of the fatty acids in a bacterial outer membrane undergo this change as acidity increases, Quivey said.

Researchers have already shown that such structural changes protect membranes, presumably by making it more difficult for acids to donate hydrogen ions to them, but they do not yet know why. Forcing hydrogen ions on other compounds gives acid its bad reputation. Remaining questions that the team will be seeking to solve over the next five years include how do longer fatty acids in membranes protect against acid specifically, and how do bacteria sense changes in acidity.

To help answer these questions, Quivey's team has genetically engineered the first and only mutant form of S. mutans with the FabM gene removed.

This FabM "knockdown" mutant is a living model that shows the exact impact of the enzyme in live bacteria. Without FabM, the mutant fills its outer membrane with other, smaller fatty acids that are much less acid resistant than those normally created via FabM, but that still provide some protection from acid. Thus, a goal is to design a treatment that would prevent S. mutans from forming both straight chain and "smaller chain" fatty acids.

As Quivey and others design next-generation antibacterial drugs, they are looking not just for a single way to stop the action of a single disease-causing enzyme, but how to shut down its three or four back-up systems. The process of cutting off genetic escape routes for bacteria applies to every trait central to the ability of the bacteria to survive and cause disease. Beyond acid durability, the team will also look at the genes and proteins that enable S. mutans to stick to teeth enamel like no other, which it does by producing a sugary polymer (plaque). Tooth decay is the result of plaque combined with acid.

Quivey's partners in the grant application were Elizabeth Grayhack, Ph.D., research associate professor of Biochemistry and Biophysics, Robert Marquis, Ph.D., professor of Microbiology and Immunology, and Eric Phizicky, Ph.D., professor of Biochemistry and Biophysics. The grant application succeeded with the NIH, Quivey said, because the team and proposal combined many years of experience in genomic projects (Grayhack and Phizicky) with extensive microbial experience (Marquis and Quivey).

As part of the grant, Grayhack and Phizicky will create a library of mutant strains for the 2,000 known S. mutans genes, with each strain having just one of the 2,000 genes shut off. They will then subject the library to acid, for example, and see which strains thrive. Knowing which gene is missing from each strain, researchers will then be able to draw conclusions about each single gene's contribution to not only to acid durability, but also to many aspects of the strep bacteria's ability to survive and cause disease.

"Down the road, the finished library will enable researchers to determine every bacterial protein involved in oral disease, to learn their exact structure and to tailor drugs that interfere with them," said Marquis. "Identifying and turning off say the top four ways in which bacteria might try to resist treatment is the team's strategy."

The Forsyth Institute has launched a new one-of-a-kind service for the research community. The Forsyth Microbial Identification Microarray Service (MIM) enables the rapid identification of bacterial species in clinical samples. The first service offering, Human Oral Microbe Identification Microarray (HOMIM), will focus on detection of bacterial profiles from the oral cavity. Researchers can use this service to compare bacterial associations in health vs. disease, monitor the effects of therapy on the oral ecology and perform microbial perturbation studies.

The Forsyth research team led by Drs. Bruce Paster and Floyd Dewhirst has used molecular analyses based on 16S rRNA sequencing to identify 550 oral bacterial species. Using this information, they have developed HOMIM, which allows the simultaneous detection of about 300 of the most prevalent oral bacterial species, in a single hybridization. This high throughput technology will allow the evaluation of species that cannot yet be grown in vitro. Information about the service can be found online at www.forsyth.org/mim.

HOMIM is available to researchers from academic institutions as well as private corporations. Researchers can submit DNA isolated from clinical samples and receive an online comprehensive analysis and report. Results can typically be obtained within days once processing has begun.

"HOMIM provides a great tool for the oral health research community," said Philip Stashenko, President and CEO of The Forsyth Institute. "The expertise of the Forsyth team is unparalleled and it can provide the scientific community with a unique opportunity to carry out global analyses of oral microbial ecology. In the future, we plan to introduce other microarrays which focus on bacteria in different body niches including the GI tract, stomach and skin."

Background:

Hundreds of different species of bacteria are able to live in the human mouth, though probably not all of them are present in the same mouth at the same time. Many of these oral bacteria have not been identified because they are impossible to grow in culture in the laboratory. Using molecular techniques, the Paster and Dewhirst laboratories have developed new tools, which do not depend on traditional culturing approaches, to hunt for oral microorganisms. Since the causative agents of oral diseases are not fully known, it is likely that some, or even many, of the novel bacterial species identified by these new methods may play important roles in disease.

The oral cavity also encompasses many surfaces, including teeth, the tongue, palate, and the oral mucosa, each coated with a plethora of bacteria. Using HOMIM, the Forsyth researchers have shown that different consortia of bacteria preferentially attach to different oral surfaces.