Mounting evidence in humans supports an etiological role for the microbiota in inflammatory
atherosclerosis.
Atherosclerosis is a progressive disease characterized by accumulation of inflammatory cells and
lipids in vascular tissue. While retention of
lipoprotein into the sub-endothelial vascular layer is believed to be the initiating stimulus leading to the development of
atherosclerosis, activation of multiple pathways related to vascular
inflammation and endothelial dysfunction sustain the process by stimulating recruitment of leukocytes and immune cells into the sub-endothelial layer. The Gram-negative oral pathogen Porphyromonas gingivalis has been associated with the development and acceleration of
atherosclerosis in humans and these observations have been validated in animal models. It has been proposed that common mechanisms of immune signaling link stimulation by
lipids and pathogens to vascular
inflammation. Despite the common outcome of P. gingivalis and
lipid feeding on
atherosclerosis progression, we established that these pro-atherogenic stimuli induced distinct gene signatures in the
ApoE-/- mouse model of
atherosclerosis. In this study, we further defined the distinct roles of dietary
lipids and P. gingivalis
infection on
atherosclerosis progression and the gut microbiota. We demonstrate that diet-induced
lipid lowering resulted in less
atherosclerotic plaque in
ApoE-/- mice compared to
ApoE-/- mice continuously fed a Western diet. However, the effect of diet-induced
lipid lowering on plaque accumulation was blunted by P. gingivalis
infection. Using principal component analysis and hierarchical clustering, we demonstrate that dietary intervention as well as P. gingivalis
infection result in distinct bacterial communities in fecal and cecal samples of
ApoE-/- mice as compared to
ApoE-/- mice continuously fed either a Western diet or a normal chow diet. Collectively, we identified distinct microbiota changes accompanying
atherosclerotic plaque, suggesting a future avenue for investigation on the impact of the gut microbiota, diet, and P. gingivalis
infection on
atherosclerosis.