Metagenomic analysis uncovers strong relationship between periodontal pathogens and vascular dysfunction in American Indian population

Periodontal disease (PD) is a well-known risk factor for cardiovascular disease (CVD) but the casual relationship is unclear. American Indians/Alaskan Natives (AI/AN) have high rate of both PD and CVD and a better understanding of how PD might affect heart health would be particularly helpful in this population. In this study, we sequenced the bacterial biofilms of periodontal (gum) pockets and used metagenomic sequencing and vascular health measurements (immune cytokine profiles and vascular flow) to determine the relationship of microbial pathogens and CVD. Twelve subjects were sequenced before and after standard periodontal treatment. Other measures taken before and after treatment included a full dental screening; serum concentration of key immune cytokines from blood samples; lipid profiles from fasting venous blood; and plasma glucose concentrations. The non-invasive Laser Doppler Fluxmetry (LDF) procedure was conducted to measures the microvascular vasodilation. We found highly significant relationships between the total abundance of 4 periodontal pathogens, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia and Treponema denticola, and the inflammatory cytokine interleukin 1 beta (IL-1{beta}) (r=0.63; p=0.009) as well as with vascular flow post sodium nitroprusside (SNP) treatment (r=p=0.006). Two bacterial species that correlated most with IL-1{beta} were F. nucleatum and P. gingivalis. IL-1{beta} has been strongly implicated as a causal factor in atherosclerosis and in periodontal bone loss. To our knowledge, this is the first direct link between abundance of specific periodontal pathogens and cardiovascular disease in humans, and suggests that these pathogens could be used as warning signs for cardiovascular risk.