The role of the oral microbiome in smoking-related cardiovascular risk: a review of the literature exploring mechanisms and pathways

Abstract

Cardiovascular disease is a leading cause of morbidity and mortality. Oral health is associated with smoking and cardiovascular outcomes, but there are gaps in knowledge of many mechanisms connecting smoking to cardiovascular risk. Therefore, the aim of this review is to synthesize literature on smoking and the oral microbiome, and smoking and cardiovascular risk/disease, respectively. A secondary aim is to identify common associations between the oral microbiome and cardiovascular risk/disease to smoking, respectively, to identify potential shared oral microbiome-associated mechanisms. We identified several oral bacteria across varying studies that were associated with smoking. Atopobium, Gemella, Megasphaera, Mycoplasma, Porphyromonas, Prevotella, Rothia, Treponema, and Veillonella were increased, while Bergeyella, Haemophilus, Lautropia, and Neisseria were decreased in the oral microbiome of smokers versus non-smokers. Several bacteria that were increased in the oral microbiome of smokers were also positively associated with cardiovascular outcomes including Porphyromonas, Prevotella, Treponema, and Veillonella. We review possible mechanisms that may link the oral microbiome to smoking and cardiovascular risk including inflammation, modulation of amino acids and lipids, and nitric oxide modulation. Our hope is this review will inform future research targeting the microbiome and smoking-related cardiovascular disease so possible microbial targets for cardiovascular risk reduction can be identified.

Keywords: Cardiovascular disease; Cardiovascular risk; Genetics; Microbiota; Oral health; Oral microbiome; Smoking.

Fig. 1

A sub-section of the genera that were cited in manuscripts that studied associations of oral bacteria with cigarette smoking, electronic cigarette smoking, and cardiovascular risk/disease, respectively. Red circles indicate a significant increase of the corresponding oral microbiome taxon to cigarette smoking, e-cigarette smoking or cardiovascular variables, while blue indicate a significantly decreased relative abundance. These figures were generated in JMP™ Version 14 Data Discovery Statistical Software. Data is shown across all oral sites and larger circles indicate more references to an increase or decrease in the specified genus. Species-level features were collapsed to the genus level for illustrative purposes. Taxa at the species and genus level used to make this figure, and the corresponding citations, can be found in Additional file 2: Table S1 (oral microbiome and smoking) and Additional file 3: Table S2 (oral microbiome and cardiovascular risk/disease). E-cigarette electronic cigarette

Fig. 2

A Shared and unique oral bacterial taxa that are decreased in association with cigarette smoking, e-cigarette smoking and CV-associated risk or disease. B Shared and unique oral bacterial taxa that are increased in association with cigarette smoking, e-cigarette smoking and CV-associated risk or disease. Bacteria summary tables from Additional file 2: Table S1 (oral microbiome and smoking) and Additional file 3: Table S2 (oral microbiome and cardiovascular risk/disease) were imported into JMP™ Version 14 Data Discovery Statistical Software, and species-level bacteria was collapsed to the genus level. If a genus-level bacterium was mentioned as increased or decreased in association with cigarette smoking, e-cigarette smoking or CVD, it was binned in the respective category. See Additional file 4: Table S3 for a summary of shared and unique bacteria. CV cardiovascular, e-cigarette electronic cigarette. Figure created with BioRender.com

Fig. 3

Schematic summarizing hypothesized pathways where the oral microbiome mediates cardiovascular risk and disease in response to smoking. A An increased RA of multiple bacteria associated with smoking including Fusobacterium, Porphyromonas, Lachnoanaerobaculum Parvimonas, Mogibacterium Streptococcus, Selenomonas, and Rothia in the oral microbiome have been positively associated with increased proinflammatory cytokine levels. A smoking-associated increase in the RA of Alloprevotella, Filifactor, Fusobacterium, Porphyromonas, Veillonella, Treponema, and Parvimonas was associated with LPS levels or biosynthesis genes, while Parvimonas was associated with CRP. Increases in local and systemic cytokines, along with elevated CRP and LPS are associated with an increased risk of CVD. B Increased RA of Rothia and Porphyromonas, both elevated in the oral cavities of smokers versus non-smokers, are potentially associated with decreased tyrosine and tryptophan levels through different hypothesized mechanisms. Prevotella RA was increased in smokers, which is positively associated with increased Apolipoprotein B levels. Both decreases in tyrosine/tryptophan and increased Apolipoprotein B is associated with increased cardiovascular risk. C An increase in the oral RA of Prevotella and Veillonella, and a decrease in the RA of Neisseria that was documented in smokers versus non-smokers is associated with decrease nitrate levels that ultimately lead to decreased nitric oxide levels. Decreased nitic oxide levels are associated with alterations in blood pressure and CVD, and may lead to a compensatory increase in oral Rothia abundance in association with smoking. Figure created with BioRender.com