Grant: CIHR Fellowship

Periodontal disease (PD) is a common condition characterized by chronic inflammation of the tissue surrounding the teeth. PD is associated with increased risk of cardiovascular disease (CVD) and thrombotic events (heart attack & stroke) even after adjustment for traditional risk factors. However, despite numerous epidemiological links, a causal role for PD in development of CVD has not been well established. Recent work by our group and others has uncovered a novel role for the gut microbiota in cardiovascular disease, whereby the microbial-derived metabolite trimethylamine (TMA) is converted to the pro-thrombotic metabolites trimethylamine-N-oxide (TMAO) by the host liver. Interestingly TMA is also significantly increased in saliva of PD patients, suggesting that cardiovascular events associated with PD may be mediated in part by microbial metabolites such as TMAO. Thus, we hypothesize that PD contributes to increased cardiovascular risks via enhanced production of pro-thrombotic metabolites by the gut microbiota. We will test this hypothesis by measuring pro-thrombotic metabolites in the blood of PD patients compared to healthy controls. We will also determine if PD associated microbes are capable of transmitting a pro-thrombotic phenotype by inoculating mice with oral plaque samples from PD patients or healthy controls. Successful completion of the proposed studies will reveal whether the gut microbiota and TMAO are likely mechanistically linked to heightened CVD risks in patients with PD. They will also define novel microbial participants associated with heightened thrombotic risks in this vulnerable population