A new study led by University of Pennsylvania researchers has found that oral microbiome is affected by diabetes, causing a shift to increase its pathogenicity.
The research—which was published last month in the journal Cell Host & Microbe—showed that changes to the oral microbiome of mice with diabetes is associated with increased inflammation and bone loss
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 as study co-author Dana Graves from the Penn’s School of Dental Medicine said, “My argument was that the appropriate studies just hadn’t been done, so I decided, we’ll do the appropriate study.”
Graves and his colleagues began by characterising the oral microbiome of diabetic mice compared to healthy mice. They found that diabetic mice had a similar oral microbiome to their healthy counterparts when they were sampled prior to developing high blood sugar levels, or hyperglycaemia. But once the diabetic mice were hyperglycaemic, 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 make that 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.
With the microbiome now implicated in causing the periodontitis, Graves et al. 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 practising good oral hygiene.