Diabetes causes shift of oral microbiome in mice, study finds

Diabetes causes shift of oral microbiome in mice, study finds

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, with implications for periodontitis. The research, published in the journal Cell Host & Microbe, 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 sceptical and decided to pursue the question, using a mouse model that mimics Type 2 diabetes.

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 signalling 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.

Article: Diabetes Enhances IL-17 Expression and Alters the Oral Microbiome to Increase Its Pathogenicity, Dana T. Graves et al., Cell Host & Microbe, doi: 10.1016/j.chom.2017.06.014, published 12 July 2017.

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