Wednesday, July 12, 2017

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."

Friday, July 7, 2017

New dental materials developed to stop degradation of demineralized dentin



 
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.