A recent study headed by researchers at the University of Pennsylvania uncovered that the oral microbiome is affected by diabetes which in turn increases its pathogenicity. Published in the journal, Cell Host & Microbe, the research showed not just that the oral microbiome of mice with diabetes altered, but that the change was linked with increased inflammation and bone loss.
Senior author on the study and vice dean of scholarship and research at Penn's School of Dental Medicine, Dana Graves, said "Up until now, there had been no concrete evidence that diabetes affects the oral microbiome”. She then went on to say, "But the studies that had been done were not rigorous”.
The European Federation of Periodontology and the American Academy of Periodontology published a report just four years ago maintaining that there is no hard evidence that diabetes is directly related to shifts in the oral microbiome. But Graves and his colleagues were sceptical and opted to pursue the subject, using a mouse model that simulates Type 2 diabetes.
"My argument was that the appropriate studies just hadn't been done, so I decided, we'll do the appropriate study" said Graves.
Graves co-authored the study with Kyle Bittinger of the Children's Hospital of Philadelphia, who aided with microbiome examination, as well as E Xiao from Peking University, who was the initial 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 carried out the bone-loss measurements at the Penn Center for Musculoskeletal Diseases.
The researchers started with exemplifying the oral microbiome of diabetic mice compared to healthy mice. They discovered that the diabetic mice had an alike oral microbiome to the healthy mice when they were tested before developing high blood sugar levels, or hyperglycaemia. However as soon as the diabetic mice were hyperglycaemic, their microbiome became distinct from their healthy counterparts, with a less diverse community of bacteria.
The diabetic mice were also found to have periodontitis, including a loss of bone supporting the teeth and amplified levels of IL-17 (a signalling molecule imperative in immune response and inflammation). In humans, high levels of IL-17 is linked to periodontal disease.
"The diabetic mice behaved similar to humans that had periodontal bone loss and increased IL-17 caused by a genetic disease," Graves disclosed.
These discoveries highlighted a link between shifts in the oral microbiome and periodontitis but couldn’t prove that the microbial shifts were accountable for the disease. To delve deeper into the connection the researchers transferred microorganisms from the diabetic mice to a set of normal germ-free mice, animals that were raised without exposure to any microbes.
These once healthy recipient mice then went on to develop bone loss. It was revealed by a micro-CT scan that they had 42 percent less bone than the mice that had received a microbial transfer from normal mice. In addition, inflammatory markers increased 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" Graves said.
Now that the microbiome has been linked to causing the periodontitis, Graves and his colleagues desired to uncover how. With evidence pointing towards inflammatory cytokines, and specifically that IL-17 played a role, the researchers replicated the microbiome transfer experiments but this time injected the diabetic donors with an anti-IL-17 antibody before the transfer. Mice that received microbiomes from the treated diabetic mice experienced far less severe bone loss in comparison to mice that received a microbiome transfer from untreated mice.
The discoveries "demonstrate unequivocally" that diabetes-induced shifts in the oral microbiome push inflammatory changes which in turn enhance bone loss in periodontitis, the authors wrote.
Although IL-17 treatment was found to be effective at decreasing bone loss in the mice, it is unlikely that it will become a rational therapeutic approach for humans due to the key part it plays in immune protection. However, Graves did note that the study underlines how essential it is that people with diabetes control their blood sugar and practice 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 glycaemic control," Graves said. "And good oral hygiene can take the risk even further down".