Oral microbiota and atherothrombotic carotid plaque vulnerability in periodontitis patients. A cross‐sectional study

Abstract

Background An increased risk of atherothrombotic vascular events has been reported in periodontitis patients. Periodontitis is associated with dysbiotic subgingival biofilms and bacteremia. Objective We hypothesized (a) that the oral microbiome is associated with the carotid microbiome and (b) that periodontitis could contribute to plaque vulnerability. The aim of this study was to determine the associations between periodontitis, the carotid microbiome, and the local innate immune response in carotid atherothrombotic plaques vulnerable to rupture. Methods In this cross‐sectional study, 45 patients admitted for carotid endarterectomy underwent a preoperative periodontal examination. The volume of intraplaque hemorrhage reflected by the hemoglobin level released in carotid‐conditioned media was considered as a criterion of carotid plaque vulnerability. Levels of antibodies against periodontal bacteria were determined in sera. The signature of the oral microbiota was assessed by microbial whole‐genome sequencing, nested PCR, and immunostaining in carotid plaque samples. Markers of neutrophil recruitment (leukotriene B4), neutrophil activation (myeloperoxidase, defensins), and cytokines were measured in carotid‐conditioned media and/or plasma. Results All patients exhibited periodontitis. One hundred and forty‐four bacterial genera were detected in the carotid microbiome. While Streptococcus was found in 84% of the carotid samples, periodontitis‐associated genera were detected in 21%. P. gingivalis DNA and gingipains were also identified in carotid samples. There were significant inverse correlations between periodontal attachment loss/serum anti‐P. gingivalis Immunoglobulin A and cytokine inhibiting neutrophils (all P < .01). There were also significant positive correlations between lipopolysaccharides, myeloperoxidase/human neutrophil peptides1‐3, and hemoglobin levels (all P < .01). Conclusions In patients at risk of stroke, the carotid plaque microbiome was highly diverse and compatible with an oral origin. Periodontitis was significantly associated with neutrophil activation markers and plaque vulnerability to rupture.

Porphyromonas gingivalis lipopolysaccharide affects the angiogenic function of endothelial progenitor cells via Akt/FoxO1 signaling

“…46 Therefore, the increased angiogenesis of EPCs caused by P. gingivalis LPS may shed light on the clinical associations of periodontitis with atherosclerotic plaque vulnerability. 47,48 Nevertheless, the clinical relevance of this study is limited due to its in vitro design and needs to be interpreted with caution. In vivo studies are highly warranted to investigate the mechanistic role of EPCs in the linkage between periodontitis and atherosclerosis at different stages.…”

“…The progressive function of EPCs is considered a contributing factor for the expansion and vulnerability of atherosclerotic plaque and subsequent atherosclerotic complications like hemorrhage, rupture, and thrombosis 46 . Therefore, the increased angiogenesis of EPCs caused by P. gingivalis LPS may shed light on the clinical associations of periodontitis with atherosclerotic plaque vulnerability 47,48 . Nevertheless, the clinical relevance of this study is limited due to its in vitro design and needs to be interpreted with caution.…”

A Cross-Talk between Diet and the Oral Microbiome: Balance of Nutrition on Inflammation and Immune System’s Response during Periodontitis

“…The Human Oral Microbiome Database provides a list and detailed description of the features and genomic information of the currently known oral cavity bacteria [32,33]. The main constituents of the oral microbiota are bacteria [4,34]. The oral bacterial community consists of six main phyla-Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Spirochaetes, and Fusobacteria-which account for 94% of the taxa detected.…”

“…It has been observed that the microbiota of healthy individuals can present up to 101 species of fungi. Candida species are the most common, followed by Cladosporium, Aureobasidium, Saccharomyces, Aspergillus, Fusarium, and Cryptococcus [11,34].…”

Periodontopathic Microbiota and Atherosclerosis: Roles of TLR-Mediated Inflammation Response

“…Similarly, Isoshima et al [ 51 ] used pyrosequence of 16S rRNA pyrosequencing to show that the majority families of the periodontal bacteria were Burkholderiales , Bacillale , and Rhizobiales , forming the soil bacterial family. Utilizing the techniques of microbial whole-genome sequencing, Brun et al [ 52 ] and Koren et al [ 53 ] showed that the most dominantly detected phyla of periopathogens in APs with periodontitis were Proteobacteria , Actinobacteria , Firmicutes , and Bacteroidetes . Current studies aiming to detect a variety of periodontal microorganisms in atherosclerotic and subgingival plaques obtained different results due to the differences in study cohorts selected, DNA detection techniques, and periodontal sample collection.…”