Four years ago, the European Federation of Periodontology and the American Academy of Periodontology reported that there was no compelling evidence that diabetes is directly linked to changes in the oral microbiome. But according to a new study from an international team of researchers, diabetes increases the pathogenicity of the oral microbiome, and the change is 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, DMSc, DDS, senior author of the study and vice dean of scholarship and research at the University of Pennsylvania School of Dental Medicine. “But the studies that had been done were not rigorous.”
The researchers began by characterizing the oral microbiome of diabetic mice compared to healthy mice. The diabetic mice had a similar oral microbiome to their health counterparts when they were sampled prior to developing 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 human beings are associated with periodontal disease. In fact, Graves noted that the diabetic mice behaved similarly to humans with periodontal bone loss and increased IL-17 caused by a genetic disease.
The findings underscored an association between changes in the oral microbiome and periodontitis but did not prove that the microbial changes were responsible for disease. To explore this connection, though, the researchers transferred microorganisms from the diabetic mice to normal germ-free mice, animals that had been raised without being exposed to any microbes.
These recipient mice also developed bone loss. A micro-CT scan revealed they had 42% less bone than mice that had received a microbial transfer from normal mice. Inflammation markers also increased in the recipients of the diabetic oral microbiome. With the microbiome implicated in causing the periodontitis, the researchers wanted to know how.
Suspecting that inflammatory cytokines, and specifically IL-17, played a role, the researchers repeated the microbiome transfer experiments, but now injecting the diabetic donors with an anti-IL-17 antibody before the transfer. Mice that received microbiomes from the treated diabetic mice had much less severe bone loss than mice that received a microbiome transfer from untreated mice.
These findings demonstrate unequivocally, the researchers said, that diabetes-induced changes in the oral microbiome drive inflammatory changes that enhance bone loss in periodontitis. But while IL-17 treatment was effective at reducing bone loss in mice, it is unlikely to be a reasonable therapeutic strategy in humans due to its key role in immune protection. Yet Graves said that the study still highlights the importance for diabetics to control blood sugar and practice good oral hygiene.
“Diabetes is one of the systemic diseases that is most closely linked to periodontal disease, but the risk is substantially ameliorated by good glycemic control,” said Graves. “And good oral hygiene can take the risk even further down.”
The study, “Diabetes Enhances IL-17 Expression and Alters the Oral Microbiome to Increase Its Pathogenicity,” was published by Cell Host & Microbe.