Drug May Guard Against Periodontitis-Related Chronic Diseases

Nov. 8, 2013 — A drug currently used to treat intestinal worms could protect people from periodontitis, an advanced gum disease, which untreated can erode the structures — including bone — that hold the teeth in the jaw. The research was published ahead of print in Antimicrobial Agents and Chemotherapy.

Current treatment for periodontitis involves scraping dental plaque, which is a polymicrobial biofilm, off of the root of the tooth. Despite this unpleasant and costly ordeal, the biofilm frequently grows back. But the investigators showed in an animal model of periodontitis that the drug Oxantel inhibits this growth by interfering with an enzyme that bacteria require for biofilm formation, says corresponding author Eric Reynolds, of the University of Melbourne, Australia. It does so in a dose-dependent manner, indicating efficacy.

The researchers began their search for a therapy for periodontitis by studying the symbioses of the periodontal pathogens, using genomics, proteomics, and metabolomics, in animal models of periodontitis. They soon found that the periodontal biofilm depended for growth on the availability of iron and heme (an iron-containing molecule related to hemoglobin), and that restricting these reduced levels of the enzyme, fumarate reductase. Since Oxantel was known to inhibit fumarate reductase in some bacteria, they then successfully tested its ability to inhibit fumarate reductase activity in Porphyromonas gingivalis, one of the major bacterial components of periodontitis biofilms. Fumarate reductase is absent from humans, making it an ideal drug target.

They also showed that Oxantel disrupted the growth of polymicrobial biofilms containing P. gingivalis, Tannerella forsythia, and Treponema denticola, a typical composition of periodontal biofilms, despite the fact that the latter alone is unaffected by Oxantel.

The researchers found that treatment with Oxantel downregulated six P. gingivalis gene products, and upregulated 22 gene products, all of which are part of a regulon (a genetic unit) that controls availability of heme.

Periodontitis affects an estimated 30-47 percent of the adult population with severe forms affecting 5-10 percent. It also increases the risks of diabetes, heart disease, stroke, arthritis, and dementia, says Reynolds. These risks arise due to the pathogenic bacteria that enter the blood stream from periodontitis, as well as from the chronic inflammation caused by this disease, he says. Additionally, periodontitis correlates with increased risk of cancers of the head and neck, the esophagus, the tongue, and the pancreas, the investigators report.

http://www.sciencedaily.com/releases/2013/11/131108112248.htm

Improving gum health may reduce heart risk

Researchers at Columbia University in New York suggest that if you look after your gums, you could also be reducing your risk of heart disease. They claim that improving dental care slows the speed with which plaque builds up in the arteries.

Writing in a recent online issue of the Journal of the American Heart Association, they report a prospective study that shows how improving gum health is linked to a clinically significant slower progression of atherosclerosis, the process where plaque builds up in arteries and increases a person’s risk ofheart disease, stroke and death.

Lead author Moïse Desvarieux, associate professor of Epidemiology at Columbia’s Mailman School of Health, says:

“These results are important because atherosclerosis progressed in parallel with both clinical periodontal disease and the bacterial profiles in the gums. This is the most direct evidence yet that modifying the periodontal bacterial profile could play a role in preventing or slowing both diseases.”

For their study, the researchers followed 420 adults aged between 60 and 76 from northern Manhattan who were taking part in the Oral Infections and Vascular Disease Epidemiology Study (INVEST).

Measuring artery thickness

All participants underwent oral infection and artery thickness exams at the start of the study and at the end of follow-up, which was a median of 3 years.

The oral infection exams retrieved a total of over 5,000 plaque samples. For each participant, the samples came from several teeth and under the gums.

The oral plaque samples were analyzed for the presence of 11 strains of bacteria known to be involved in periodontal disease and seven control bacteria.

Samples of fluid from around the gums were also taken and assessed for levels of Interleukin-1β, a marker ofinflammation.

The extent of atherosclerosis, was assessed using high-resolution ultrasound scans to measure artery thickness or intima-medial thickness (IMT) in both carotid arteries.

The results showed that both improved gum health and a reduction in the proportion of bacteria linked to periodontal disease correlated to a slower progression of atherosclerosis, as measured by IMT.

These results did not change significantly when adjusted for factors that could influence them, such as body mass index, cholesterol levels, diabetes and smoking.

Previous studies have linked an increase in carotid IMT of 0.033 mm per year (about 0.1 mm over 3 years), to a more than double increase in risk of heart attack and stroke.

In this study, the participants whose gum health got worse over the 3 years showed a 0.1 mm increase in carotid IMT, compared with the participants whose gum health improved.

Co-author Panos N. Papapanou, professor at Columbia’s College of Dental Medicine, says:

“Our results show a clear relationship between what is happening in the mouth and thickening of the carotid artery, even before the onset of full-fledged periodontal disease. This suggests that incipient periodontal disease should not be ignored.”

Atherosclerosis and periodontal infections

Although the researchers did not look into how bacteria in the mouth can lead to atherosclerosis, one theory suggested by animal studies is they increase inflammatory markers, which can trigger or worsen the inflammation in atherosclerosis.

In a previous study that took measures at one point in time, the team had already found that higher levels of disease-causing bacteria were linked to thicker carotid IMT. This new study builds on those results by looking at the participants over time.

Prof. Desvarieux adds:

“It is critical that we continue to follow these patients to see if the relationship between periodontal infections and atherosclerosis carries over to clinical events like heart attack and stroke and test if modifying the periodontal flora will slow the progression of atherosclerosis.”

Funds from the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke (NINDS), the Institut National de la Santé et de la Recherche Medicale (INSERM), among others, helped finance the study.

In 2010, UK researchers reported that gum bacteria can increase risk of heart attack and heart disease, because the same bacteria that cause dental plaque can escape from the mouth into the bloodstream and trigger clots.

http://www.medicalnewstoday.com/articles/268325.php