Diabetes Causes a Shift in Oral Microbiome that can Develop Periodontitis

Diabetes Causes a Shift in Oral Microbiome that can Develop Periodontitis

Pennsylvania, USA- Researchers at the University of Pennslyvania have found that the oral microbiome is affected by diabetes, causing a shift to increase its pathogenicity. The research was published in the journal Cell Host & Microbe and it showed that the oral microbiome of mice with diabetes shifted and the change was associated with increased inflammation and bone loss.

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

Four years ago, the European Federation of Periodontology and the American Academy of Periodontology issued a report saying there is no imperative evidence that diabetes is directly linked to changes in the oral microbiome. Graves and his colleagues were skeptical and decided to pursue the question using a mouse model that mimics Type 2 diabetes. She argued that the appropriate study hadn't been done yet so she decided that they would do the appropriate study. 

Graves co-authored the study with Kyle Bittinger of the Children's Hospital of Philadelphia, who helped 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 worked 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 their study by looking at the oral microbiome of diabetic mice compared to healthy mice. They found that the diabetic mice had a similar oral microbiome to the healthy mice when they were sampled prior to developing high blood sugar levels, or hyperglycemia. But, once they were hyperglycemic, their microbiome became distinct from the healthy mice, with a less diverse community of bacteria. 

They also noticed that the diabetic mice had peridontitis and a loss of bone supporting the teeth with increased levels of 1L-17, which is a signaling molecule important in immune response and inflammation. 

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

The recipient mice also developed bone loss. A micro-CT scan showed 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.

Graves said that they 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.

Now that Graves and collegues knew that the microbiome was causing the peridontitis they wanted to know how. They had a feeling that inflammatory cytokines, specficially IL-17, played a role, they repeated the microbiome transfer experiments but this time they injected 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 undeniably show that diabetes-induced changes in the oral microbiome cause inflammatory changes that enhance bone loss in periodontitis, the authors wrote.

Even though IL-17 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. 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 mentioned that the study highlights the importance for people with diabetes of controlling blood sugar and practicing good oral hygiene.

Diabetes is one of the diseases that is most closely linked to peridontal disease and the risk can be substantially improved by good glycemic control, along with having good oral hygiene, said Graves. 

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