History of gum disease increases cancer risk in older women

Postmenopausal women who have a history of gum disease also have a higher risk of cancer, according to a new study of more than 65,000 women.

The study, led by researchers at the University at Buffalo, is the first national study of its kind involving U.S. women, and the first to focus specifically on older women. It's also the first study to find an association between periodontal disease and gallbladder cancer risk in women or men. The findings were published today (Aug. 1) in the journal Cancer Epidemiology, Biomarkers & Prevention.

"This study is the first national study focused on women, particularly older women," said Jean Wactawski-Wende, the study's senior author.

"Our study was sufficiently large and detailed enough to examine not just overall risk of cancer among older women with periodontal disease, but also to provide useful information on a number of cancer-specific sites," added Wactawski-Wende, dean of UB's School of Public Health and Health Professions and a professor of epidemiology and environmental health.

The study included 65,869 postmenopausal women enrolled in the Women's Health Initiative, an ongoing national prospective study designed to investigate factors affecting disease and death risk in older American women. The average age of the participants was 68, and most were non-Hispanic white women.

As part of a follow-up health questionnaire, participants were asked "Has a dentist or dental hygienist ever told you that you had periodontal or gum disease?"

Women who reported a history of gum disease had a 14 percent increased risk of overall cancer. Of the 7,149 cancers that occurred in the study participants, the majority -- or 2,416 -- were breast cancer.

"There is increasing evidence that periodontal disease may be linked to an increased cancer risk and this association warrants further investigation," said the paper's first author, Ngozi Nwizu, who worked on the research while completing her residency in oral and maxillofacial pathology in UB's School of Dental Medicine and her doctorate in pathology (cancer epidemiology) at UB's Roswell Park Cancer Institute Graduate Division. Nwizu is now an assistant professor of oral and maxillofacial pathology at the University of Texas Health Science Center at Houston.

The risk associated with periodontal disease was highest for esophageal cancer, the researchers reported. "The esophagus is in close proximity to the oral cavity, and so periodontal pathogens may more easily gain access to and infect the esophageal mucosa and promote cancer risk at that site," Wactawski-Wende said.

Gallbladder cancer risk also was high in women who reported a history of gum disease. "Chronic inflammation has also been implicated in gallbladder cancer, but there has been no data on the association between periodontal disease and gallbladder risk. Ours is the first study to report on such an association," Nwizu said.

The esophageal and gallbladder cancer findings are significant, Nwizu said. "Esophageal cancer ranks among the most deadly cancers and its etiology is not well known, but chronic inflammation has been implicated," she said.

"Certain periodontal bacteria have been shown to promote inflammation even in tiny amounts, and these bacteria have been isolated from many organ systems and some cancers including esophageal cancers. It is important to establish if periodontal disease is an important risk of esophageal cancer, so that appropriate preventive measures can be promoted."

Periodontal disease also was associated with total cancer risk among former and current smokers.
The findings for this particular age group are significant because they offer a window into disease in a population of Americans that continues to increase as people live longer lives.

"The elderly are more disproportionately affected by periodontal disease than other age groups, and for most types of cancers, the process of carcinogenesis usually occurs over many years," said Nwizu. "So the adverse effects of periodontal disease are more likely to be seen among postmenopausal women, simply because of their older age."

Diabetes causes shift in oral microbiome that fosters periodontitis

A new study led by University of Pennsylvania researchers has found that the oral microbiome is affected by diabetes, causing a shift to increase its pathogenicity. The research, published in the journal Cell Host & Microbe this week, not only showed that the oral microbiome of mice with diabetes shifted but that the change was associated with increased inflammation and bone loss. 

"Up until now, there had been no concrete evidence that diabetes affects the oral microbiome," said Dana Graves, senior author on the new study and vice dean of scholarship and research at Penn's School of Dental Medicine. "But the studies that had been done were not rigorous."

Just four years ago, the European Federation of Periodontology and the American Academy of Periodontology issued a report stating there is no compelling evidence that diabetes is directly linked to changes in the oral microbiome. But Graves and colleagues were skeptical and decided to pursue the question, using a mouse model that mimics Type 2 diabetes.

"My argument was that the appropriate studies just hadn't been done, so I decided, We'll do the appropriate study," Graves said.

Graves co-authored the study with Kyle Bittinger of the Children's Hospital of Philadelphia, who assisted with microbiome analysis, along with E Xiao from Peking University, who was the first author, and co-authors from the University of São Paulo, Sichuan University, the Federal University of Minas Gerais and the University of Capinas. The authors consulted with Daniel Beiting of Penn Vet's Center for Host-Microbial Interactions and did the bone-loss measurements at the Penn Center for Musculoskeletal Diseases. 

The researchers began by characterizing the oral microbiome of diabetic mice compared to healthy mice. They found that the diabetic mice had a similar oral microbiome to their healthy counterparts when they were sampled prior to developing high blood sugar levels, or hyperglycemia. But, once the diabetic mice were hyperglycemic, their microbiome became distinct from their normal littermates, with a less diverse community of bacteria.

The diabetic mice also had periodontitis, including a loss of bone supporting the teeth, and increased levels of IL-17, a signaling molecule important in immune response and inflammation. Increased levels of IL-17 in humans are associated with periodontal disease.

"The diabetic mice behaved similar to humans that had periodontal bone loss and increased IL-17 caused by a genetic disease," Graves said.

The findings underscored an association between changes in the oral microbiome and periodontitis but didn't prove that the microbial changes were responsible for disease. To drill in on the connection, the researchers transferred microorganisms from the diabetic mice to normal germ-free mice, animals that have been raised without being exposed to any microbes. 

These recipient mice also developed bone loss. A micro-CT scan revealed they had 42 percent less bone than mice that had received a microbial transfer from normal mice. Markers of inflammation also went up in the recipients of the diabetic oral microbiome.

"We were able to induce the rapid bone loss characteristic of the diabetic group into a normal group of animals simply by transferring the oral microbiome," said Graves.

With the microbiome now implicated in causing the periodontitis, Graves and colleagues wanted to know how. Suspecting that inflammatory cytokines, and specifically IL-17, played a role, the researchers repeated the microbiome transfer experiments, this time injecting the diabetic donors with an anti-IL-17 antibody prior to the transfer. Mice that received microbiomes from the treated diabetic mice had much less severe bone loss compared to mice that received a microbiome transfer from untreated mice. 

The findings "demonstrate unequivocally" that diabetes-induced changes in the oral microbiome drive inflammatory changes that enhance bone loss in periodontitis, the authors wrote.

Though IL-17 treatment was effective at reducing bone loss in the mice, it is unlikely to be a reasonable therapeutic strategy in humans due to its key role in immune protection. But Graves noted that the study highlights the importance for people with diabetes of controlling blood sugar and practicing good oral hygiene.

"Diabetes is one of the systemic disease that is most closely linked to periodontal disease, but the risk is substantially ameliorated by good glycemic control," he said. "And good oral hygiene can take the risk even further down."

New dental materials developed to stop degradation of demineralized dentin

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A: Demineralized dentin with a number of collagen fibres, that if not preserved and remineralized, these can be degraded by the action of the dentinal proteolytic enzymes. B: Dentin treated with resin with fluoride-containing bioactive glass, which presents mineral precipitations – signs of remineralization.

 

Credit: Image courtesy of Asociación RUVID

 

Salvatore Sauro, Professor of dental biomaterials and minimally invasive dentistry at CEU Cardenal Herrera University, in Spain, has collaborated with several researchers from Finland, Brazil, Belgium, Germany and the UK on the development of innovative dental biomaterials for the regeneration of dental hard tissues.

Bacterial plaque causes tooth decay due to acids produced by different bacteria species; this has trigged an intense research activity for the development of novel restorative biomaterials with protective and self-healing remineralizing properties. In this new study, Salvatore Sauro, a professor of CEU Cardenal Herrera University (Spain) specialized in the development of innovative dental biomaterials, has collaborated with several researchers from Finland, Brazil, Belgium, Germany and the United Kingdom in order to accomplish this target. Indeed, this international group of research generated two new dental restorative biomaterials containing bioactive glasses, and assessed their effectiveness in reducing the enzymatic auto-degradation of collagen fibres and evoking their remineralization.

The aim of the study was to evaluate the inhibition of endogenous proteolytic enzymes of dentin and the remineralization induced by two different innovative experimental resins containing bioactive glasses: one containing micro-particles of Bioglass 45S5 and the other one containing micro-particles of an experimental bioactive glass enriched with fluoride and high amount of phosphates. Their anti-degradation effects was evaluated on completely demineralized human dentin specimens after immersion in artificial saliva for a period of thirty days by means of an immunohistochemical process. The remineralization evoked by such experimental bioactive resins was also evaluated by means of infrared spectroscopy and scanning electron microscopy.

Greater effectiveness with fluoride and phosphates

According to Professor Salvatore Sauro and his co-authors, " the resin-based material containing the experimental bioactive glass enriched with fluoride and phosphates resulted to be more efficient in inhibiting the enzymatic-mediated degradation of demineralized dentine collagen, and more bioactive than the one containing Bioglass 45S5. This was mainly due to the fluoride ions as well as to the large amount of phosphates released by the material, which accelerated dentin remineralization and reduced the degradation of demineralized dentin collagen via inhibition of matrix metalloproteinases and cysteine cathepsins.

This type of experimental bioactive material would therefore be more suitable for the development of new restorative dental materials for the clinical treatment of the dental caries.

Publication in the Journal of Dental Research

Professor Sauro perform his research activity mainly at CEU Cardenal Herrera University, (Spain) as well as at King's College London (UK) where he has an honorary position as research senior lecturer. He spends most of his time in the development of minimally invasive treatments and therapeutic bioactive dental composites for the treatment and restoration of caries affected dentin, such as those tested in this study -- which seem to be able to prevent the degradation of dentin collagen and evoke the remineralization of demineralized dental tissues. In this study, Dr Salvatore Sauro collaborated with researchers from the Department of Restorative Dentistry of the University of Turku (Finland); the Faculty of Dentistry of the University of Fortaleza (Brazil); the Biomaterials Group of the University of Ghent (Belgium); the Friedrich Schiller University of Jena (Germany); and the Dental Institute of King's College London (United Kingdom), institution of which Salvatore Sauro is a Visiting Senior Lecturer.

The study is published in the Journal of Dental Research.

Blocking yeast-bacteria interaction may prevent severe biofilms that cause childhood tooth decay

Though most tooth decay can be blamed on bacteria, such as Streptococcus mutans, the fungus Candida albicans may be a joint culprit in an alarmingly common form of severe tooth decay affecting toddlers known as early childhood caries.

In earlier research, a team from the University of Pennsylvania School of Dental Medicine had found that C. albicans, a type of yeast, took advantage of an enzyme produced by S. mutans to form a particularly intractable biofilm. In a new study, the researchers have pinpointed the surface molecules on the fungus that interact with the bacterially-derived protein. Blocking that interaction impaired the ability of yeast to form a biofilm with S. mutans on the tooth surface, pointing to a novel therapeutic strategy.

"Instead of just targeting bacteria to treat early childhood caries, we may also want to target the fungi," said Hyun (Michel) Koo, senior author on the study and a professor in the Department of Orthodontics and Divisions of Pediatric Dentistry and Community Oral Health. "Our data provide hints that you might not need to use a broad spectrum antimicrobial and might be able to target the enzyme or cell wall of the fungi to disrupt the plaque biofilm formation."

Koo collaborated on the work with Penn Dental's Geelsu Hwang, the first author and a research assistant professor, as well as Yuan Liu, Dongyeop Kim and Yong Li. Damian J. Krysan of the University of Rochester was also a coauthor.

The research appears in the journal PLOS Pathogens.

Candida can't effectively form plaque biofilms on teeth on its own nor can it bind S. mutans, unless in the presence of sugar. Young children who consume sugary beverages and foods in excess are at risk of developing early childhood caries. Koo's team had previously discovered that an enzyme, GftB, secreted by S. mutans, uses sugar from the diet to manufacture glue-like polymers called glucans. Candida promotes this process, resulting in a sticky biofilm that allows the yeast to adhere to teeth and to bind to S. mutans.

The researchers suspected that the outer portion of the Candida cell wall, composed of molecules called mannans, might be involved in binding GftB. To gain a more detailed understanding of the interaction between the yeast and the enzyme, the researchers measured the binding strength between various mutant Candida strains and GtfB using biophysical methods. Such measurements were developed by Hwang, who has a background in engineering and is applying his unique expertise to advance dental science.

Koo, Hwang and colleagues found that the enzyme bound much more weakly to mutants that lacked components of the mannan layer than the wild-type Candida. The team next looked at the abilities of the mutant Candida to form biofilms with S. mutans in a laboratory assay. The mutants that had impaired binding with GftB were mostly unable to form biofilms with S. mutans, resulting in significantly fewer Candida cells and reduced production of the sticky glucans molecules.

Using another biophysical technique, the researchers tested how stable the biofilms were when attached to a tooth-like surface. While low-shear stress, roughly equivalent to the force generated by taking a drink of water, removed only a quarter of the wild-type biofilm, the same force removed 70 percent of the biofilms with mutant Candida. When the forces were increased to the equivalent of a vigorous mouth rinse, the mutant biofilms were almost completely dislodged.

To ensure their findings translated to in vivo conditions, they examined biofilm formation in a rodent model that can mimic the development of early childhood caries. When animals were infected with both S. mutans and either the wild type or defective mutant yeast strains, the researchers observed clear differences. While biofilm formation was abundant if the wild-type yeast was used, it was substantially reduced in animals infected with the mutant strain. A more precise analysis revealed that the these defective biofilms completely lacked viable Candida cells and S. mutans were reduced by more than five-fold.

The findings point to a new direction for treatment of early childhood caries. The current standard of care, beyond the use of fluoride as a preventive approach, is to target only the bacteria with antimicrobials, or to use surgical interventions if the tooth decay has become too severe.

"This disease affects 23 percent of children in the United States and even more worldwide," said Koo. "In addition to fluoride, we desperately need an agent that can target the disease-causing biofilms and in this case not only the bacterial component but also the Candida."

Koo and colleagues are now working on novel therapeutic approaches for targeted interventions, which can be potentially developed for clinical use.

Visiting virtual beach improves patient experiences during dental procedures

Imagine walking along a South Devon beach on a lovely day. The waves are lapping on the shore, rabbits are scurrying in the undergrowth, and the bells of the local church are mingling with the calls of the seagulls. Then, as you turn to continue along the coast path feeling calm and relaxed you suddenly hear your dentist say "Fine, all done, you can take the headset off now". For patients at one dental practice in Devon, England, such Virtual Reality encounters are resulting in demonstrably better experiences in the dentist's chair. 

A link to what the patient sees is here - https://youtu.be/n5kjETt8cZI.

In a study published today (Wednesday 14th June 2017) in the journal Environment & Behaviour, a team of researchers at the Universities of Plymouth, Exeter and Birmingham worked with Torrington Dental Practice in Devon to find out whether experiences like these could improve the patient's experience during routine dental procedures, such as fillings and tooth extractions. 

Patients, who had agreed to take part in the study were randomly allocated to one of three conditions: a) standard care (i.e. normal practice), b) a virtual walk around Wembury beach in Devon (using a headset and handheld controller), or c) a walk around an anonymous virtual reality city. Results found that those who 'walked' around Wembury were less anxious, experienced less pain, and had more positive recollections of their treatment a week later, than those in the standard care condition. These benefits were not found for those who walked around the virtual city. 

Dr. Karin Tanja-Dijkstra was the lead author of the study. She said: "The use of virtual reality in health care settings is on the rise but we need more rigorous evidence of whether it actually improves patient experiences. Our research demonstrates that under the right conditions, this technology can be used to help both patients and practitioners."

The authors of the research stress that the type of virtual reality environment the patient visits is important. Virtual Wembury was created by Professor Bob Stone and colleagues at the University of Birmingham, and the fact that only patients who visited Wembury, and not the virtual city, had better experiences than standard care is consistent with a growing body of work that shows that natural environments, and marine environments in particular, can help reduce stress and anxiety. 

Co-author Dr. Mathew White from the University of Exeter explained: "We have done a lot of work recently which suggests that people are happiest and most relaxed when they are at the seaside. So it seemed only natural to investigate whether we could "bottle" this experience and use it to help people in potentially stressful healthcare contexts." 

Dr Sabine Pahl, the project's coordinator at the University of Plymouth, added: "That walking around the virtual city did not improve outcomes shows that merely distracting the patients isn't enough, the environment for a patient's visit needs to be welcoming and relaxing. It would be interesting to apply this approach to other contexts in which people cannot easily access real nature such as the workplace or other healthcare situations."

The Torrington Practice dentist involved in the research, Melissa Auvray, agreed: "The level of positive feedback we got from patients visiting Virtual Wembury was fantastic. Of course, as dentists we do our very best to make the patient feel as comfortable as possible but we are always on the look out for new ways to improve their experiences." 

Professor David Moles from the University of Plymouth added "This research is one of a number of initiatives we at Plymouth University Peninsula School of Dentistry have been working on alongside the fabulous team at Torrington Dental Practice and it clearly demonstrates the benefits that can be achieved when academics work in partnership with clinicians in order to address problems that really matter to patients."

The team are hoping to now investigate whether Virtual Wembury can help patients in other medical contexts and whether certain additions to the virtual environment could make the experience even better.

Study: Use of prefabricated blood vessels may revolutionize root canals

While root canals are effective in saving a tooth that has become infected or decayed, this age-old procedure may cause teeth to become brittle and susceptible to fracture over time. Now researchers at OHSU in Portland, Oregon, have developed a process by which they can engineer new blood vessels in teeth, creating better long-term outcomes for patients and clinicians.

Their findings will publish online in the journal Scientific Reports on June 12, 2017. 

More than 15 million root canals are conducted annually in the United States. The current procedure involves removing infected dental tissues and replacing them with synthetic biomaterials covered by a protective crown. 

"This process eliminates the tooth's blood and nerve supply, rendering it lifeless and void of any biological response or defense mechanism. Without this functionality, adult teeth may be lost much sooner, which can result in much greater concerns, such as the need for dentures or dental implants," says principal investigator Luiz Bertassoni, D.D.S., Ph.D., assistant professor of restorative dentistry in the OHSU School of Dentistry, and assistant professor of biomedical engineering in the OHSU School of Medicine.

To address this issue, Bertassoni and colleagues used a 3D printing-inspired process -- based on their previous work fabricating artificial capillaries -- to create blood vessels in the lab. They placed a fiber mold made of sugar molecules across the root canal of extracted human teeth and injected a gel-like material, similar to proteins found in the body, filled with dental pulp cells. The researchers removed the fiber to make a long microchannel in the root canal and inserted endothelial cells isolated from the interior lining of blood vessels. After seven days, dentin-producing cells proliferated near the tooth walls and artificial blood vessels formed inside the tooth.

"This result proves that fabrication of artificial blood vessels can be a highly effective strategy for fully regenerating the function of teeth," says Bertassoni, who also serves as an honorary lecturer in Bioengineering at University of Sydney-School of Dentistry. "We believe that this finding may change the way that root canal treatments are done in the future."

Common periodontal pathogen may interfere with conception in women

According to a study carried out at the University of Helsinki, Finland, a common periodontal pathogen may delay conception in young women. This finding is novel: previous studies have shown that periodontal diseases may be a risk for general health, but no data on the influence of periodontal bacteria on conception or becoming pregnant have been available.

"Our results encourage young women of fertile age to take care of their oral health and attend periodontal evaluations regularly", says periodontist and researcher Susanna Paju, University of Helsinki.

Study population comprised 256 healthy non-pregnant women (mean age 29.2 years, range 19 to 42) who had discontinued contraception in order to become pregnant. They were enrolled from the general community from Southern Finland. Clinical oral and gynecological examinations were performed. Detection of major periodontal pathogens in saliva and analysis of serum and saliva antibodies against major periodontal pathogens as well as a vaginal swab for the diagnosis of bacterial vaginosis at baseline were carried out.

Subjects were followed-up to establish whether they did or did not become pregnant during the observation period of 12 months.

Porphyromonas gingivalis, a bacterium associated with periodontal diseases, was significantly more frequently detected in the saliva among women who did not become pregnant during the one-year follow-up period than among those who did. The levels of salivary and serum antibodies against this pathogen were also significantly higher in women who did not become pregnant.

Statistical analysis showed that the finding was independent of other risk factors contributing to conception, such as age, current smoking, socioeconomic status, bacterial vaginosis, previous deliveries, or clinical periodontal disease.

Women who had P. gingivalis in the saliva and higher saliva or serum antibody concentrations against this bacterium had a 3-fold hazard for not becoming pregnant compared to their counterparts. Increased hazard was nearly to 4-fold if more than one of these qualities and clinical signs of periodontitis were present.

"Our study does not answer the question on possible reasons for infertility but it shows that periodontal bacteria may have a systemic effect even in lower amounts, and even before clear clinical signs of gum disease can be seen", says Dr. Paju. "More studies are needed to explain the mechanisms behind this association."

Infertility is a major concern, and increasing healthcare resources are needed for infertility treatments. More attention should be paid to the potential effects of common periodontal diseases on general health. Young women are encouraged to take care of their oral health and maintain good oral hygiene also when they are planning pregnancy, suggests Dr. Paju.