Presence of periodontal pathogenic bacteria in blood of patients with coronary artery disease

Abstract

It has been hypothesised that oral bacteria can migrate, through the blood, from the mouth to the arterial plaques, thus exacerbating atherosclerosis. This study compared bacteria present in the peripheral blood of individuals with and without coronary artery disease (CAD). RNA sequences obtained from blood were downloaded from GEO (GSE58150). Eight patients with coronary artery calcification (CAC) scoring > 500 and eight healthy individuals were analysed. After conducting quality control, the sequences were aligned to the hg38 reference genome using Hisat2. Bacterial taxa were analysed by inputting the unmapped sequences into Kraken. Ecological indices were calculated using Vegan. The package DESeq2 was used to compare the counts of bacteria per standard rank between groups. A total of 51 species were found only in patients with CAD and 41 were exclusively present in healthy individuals. The counts of one phylum, one class, three orders, two families and one genus were significantly different between the analysed groups (p < 0.00032, FDR < 10%), including the orders Cardiobacteriales, Corynebacteriales and Fusobacteriales. Twenty-three bacterial species belonging to the subgingival plaque bacterial complexes were also identified in the blood of individuals from both the groups; Fusobacterium nucleatum was significantly less frequent in patients with CAD (p = 0.0012, FDR = 4.8%). Furthermore, the frequency of another 11 bacteria differed significantly among patients with CAD than that among healthy individuals (p < 0.0030, FDR < 10%). These bacteria have not been previously reported in patients with atherosclerosis and periodontitis. The presence of members of the subgingival plaque bacterial complexes in the blood of patients with CAC supports the hypothesis that the periodontopathogens can be disseminated through the blood flow to other body parts where they may enhance inflammatory processes that can lead to the development or exacerbation of atherosclerosis.

Figure 1

Workflow of data analysis. RNA sequences were mapped to the GRCh38 human reference genome and unmapped reads were fed into Kraken to classify the reads to bacterial taxa. The richness and diversity indices were obtained using Vegan.

Figure 2

Number of (a) species, (b) genera and (c) families common to both CAD and healthy groups. The healthy group has a major amount of each of this taxon.

Figure 3

(A) Box plot of the mean number of species in the CAD and healthy groups. (B) Comparison of Simpson evenness between the CAD and healthy groups.

Figure 4

Taxonomic composition and relative abundance of the bacteria in CAD and healthy groups. (A) The most abundant phylum identified in the study, and (B) the 12 species differing significantly between the CAD and healthy groups.