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

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.

Attitudes of general and specialist French practitioners toward stage III-IV grade C periodontitis with familial aggregation.

The aim of this cross-sectional convenience sample survey was to assess attitudes of French dentists regarding stage III-IV grade C periodontitis in systemically healthy individuals. Among 225 dentists, 85.1% informed patients of the familial nature of periodontitis including 27.3% that recommended a consultation for the family. When dealing with a child who presented with severe periodontitis, 42.2% of the respondents did not advise examination of the parents. In addition, 39.1% of practitioners did not consider it possible to establish a family consultation. Finally, family factors are not often considered by French practitioners in the management of grade C periodontitis.

[Periodontitis : An underestimated risk of cardiovascular diseases]. / La parodontite : un risque sous-estimé des maladies cardiovasculaires.

Epidemiological studies have identified periodontitis as a contributing factor to cardiovascular risk. Periodontitis is a chronic inflammatory disease that affects the tissues supporting the teeth. Although the nature of the association between periodontitis and cardiovascular disease (CVD) remains to be defined, the low-grade systemic inflammation and chronic bacteremia associated with periodontitis appear to be involved in the development of atherosclerosis and associated cardiovascular pathologies. Periodontal treatment has been shown to improve cardiovascular health parameters. A bidirectional preventive approach, involving the management of both periodontitis and cardiovascular risk factors, could lead to a reduction in morbidity and mortality related to cardiovascular disease.

Title: La parodontite : un risque sous-estimé des maladies cardiovasculaires. Abstract: Les études épidémiologiques identifient la parodontite, maladie inflammatoire chronique des tissus de soutien des dents, comme un facteur contribuant au risque cardiovasculaire. Bien que la nature de l'association entre parodontite et maladies cardio-vasculaires (MCV) reste à définir (causalité ou corrélation), l'inflammation systémique de bas grade et les bactériémies chroniques qui sont associées aux parodontites apparaissent impliquées dans le développement de l'athérosclérose et des maladies cardio-vasculaires associées. Le traitement parodontal semble contribuer à l'amélioration des paramètres de la santé cardiovasculaire. Dès lors, une approche de prévention bidirectionnelle, impliquant à la fois la gestion de la parodontite et des facteurs de risque cardiovasculaire, pourrait permettre une réduction de la morbidité et de la mortalité liées aux MCV.

Perceptions regarding the use of a three-dimensionally-printed manufactured educational simulator for periodontal treatment of intraosseous and interradicular lesions.

PURPOSE/OBJECTIVES: Treating intraosseous lesions (IOLs) and interradicular bone lesions (IRLs) is an extremely technical dental procedure in periodontics. Instrumentation of these lesions is often perceived as difficult by students and inexperienced dentists before they perform a certain number of procedures on patients in the clinic. The aim of this article is to evaluate a cost-effective three-dimensional (3D)-printed educational simulator for the periodontal treatment of IOLs/IRLs (including scaling, incisions and sutures). METHODS: The simulators were first developed digitally, and then manufactured using printable resins and specific materials; finally, they were assembled using different bonding systems. To evaluate the simulators, assessments were gathered from two target populations: undergraduate students and periodontics experts. These individuals tested the simulator and completed a cross-sectional questionnaire based on a Likert scale with comparative and pedagogical items scored from one to five. The purpose of the questionnaire was to compare our simulator to clinical reality (i.e., operation on human jaws) and to an animal simulator (i.e., simulation of porcine jaws). The results are expressed as the mean and standard deviation and were statistically analyzed with the Wilcoxon signed-rank test. RESULTS: Overall, the results were satisfactory for both groups of testers (4.70 and 4.61 out of five for students and experts, respectively, for global satisfaction). CONCLUSIONS: The overall educational relevance of the simulator designed herein highlights the fact that 3D-printed educational simulators could enable efficient cognitive-functional learning for clinical IOL/IRL treatment.

Periodontitis in ischemic stroke: impact of Porphyromonas gingivalis on thrombus composition and ischemic stroke outcomes.

Background: Periodontitis is associated with an increased risk of ischemic stroke, but the mechanisms underlying this association remain unclear. Objectives: Our objective was to determine whether Porphyromonas gingivalis (Pg), a periodontal bacterium, could be detected within thrombus aspirates, modify thrombus composition, and endovascular therapy responses. Methods: The presence of Pg gingipain in 175 consecutive thrombi from patients with large vessel occlusion stroke enrolled in the multicenter research cohort compoCLOT was investigated by immunostaining. Thrombus blood cell composition according to gingipain status was analyzed in a subset of 63 patients. Results: Pg gingipain immunostaining was positive in 33.7% of thrombi (95% CI, 26.7%-40.8%). The percentage of near to complete reperfusion (modified Thrombolysis in Cerebral Infarction Score 2c/3) at the end of the procedure was lower in the Pgpos group than the Pgneg group (39.0% vs 57.8% respectively; adjusted odds ratio, 0.38; 95% CI, 0.19-0.77). At 3 months, 35.7% of patients in the Pgpos group had a favorable neurological outcome vs 49.5% in the Pgneg group (odds ratio, 0.65; 95% CI, 0.30-1.40). Quantitative analysis of a subset of 63 thrombi showed that neutrophil elastase content was significantly (P < .05) higher in Pgpos thrombi than in Pgneg thrombi. Conclusion: Our results indicate that intrathrombus Pg gingipain is associated with increased neutrophil content and resistance to endovascular therapy.

Innovative application of nested PCR for detection of Porphyromonas gingivalis in human highly calcified atherothrombotic plaques.

Atherothrombosis, leading to stroke and myocardial infarction, is responsible for most of the deaths in the world. An increased risk of atherothrombotic vascular events has been reported in patients with periodontitis. Periodontitis is a chronic multifactorial inflammatory disease, which involves a dysbiotic microbiota, and leads to a progressive destruction of the tooth-supporting apparatus. Transcient periodontal pathogen blood translocation, mainly bacteremia, has been associated with the severity of gingival inflammation. The identification of periodontal bacteria within atherothrombotic plaques is challenging and unpredictable. This review aims to summarize existing molecular technics for identifying periodontal microbiota in human atherothrombotic samples. A secondary objective is to describe a protocol for the identification of Porphyromonas gingivalis from highly calcified, atherothrombotic human samples that is based on our experience in translational cardiovascular research. Compared to direct real-time PCR, our protocol based on nested PCR has increased the detection of Porphyromonas gingivalis by 22.2% with good specificity.

Intraplaque hemorrhage, a potential consequence of periodontal bacteria gathering in human carotid atherothrombosis.

Periodontal diseases are multifactorial inflammatory diseases, caused by a bacterial biofilm involving both innate and adaptative immunity, characterized by the destruction of tooth-supporting tissues. In the context of periodontitis, the spread of weak pathogenic bacteria into the bloodstream has been described. These bacteria will preferentially localize to existing clot within the circulation. Atherothrombosis of the carotid arteries is a local pathology and a common cause of cerebral infarction. Intraplaque hemorrhages render the lesion more prone to clinical complications such as stroke. The main objective of this study is to explore the biological relationship between carotid intraplaque hemorrhage and periodontal diseases. This study included consecutive patients with symptomatic or asymptomatic carotid stenosis, admitted for endarterectomy surgical procedure (n=41). In conditioned media of the carotid samples collected, markers of neutrophil activation (myeloperoxidase or MPO, DNA-MPO complexes) and hemoglobin were quantified. To investigate the presence of DNA from periodontal bacteria in atherosclerotic plaque, PCR analysis using specific primers was performed. Our preliminary results indicate an association between neutrophil activation and intraplaque hemorrhages, reflected by the release of MPO (p<0,01) and MPO-DNA complexes (p<0,05). Presence of DNA from periodontitis-associated bacteria was found in 32/41 (78%) atheromatous plaque samples. More specifically, DNA from Pg, Tf, Pi, Aa was found in 46%, 24%, 34% and 68% of the samples, respectively. Hemoglobin levels were higher in conditioned media in carotid samples where the bacteria were found, but this was not statistically significant. Our data confirm the relationship between intraplaque hemorrhage and neutrophil activation. In addition, the presence of periodontal bacteria DNA in carotid atheromatous plaque, may contribute to this activation. Further analysis is needed to fully explore the raw data and specimens.

Different sympathetic pathways control the metabolism of distinct bone envelopes.

Bone remodeling, the mechanism that modulates bone mass adaptation, is controlled by the sympathetic nervous system through the catecholaminergic pathway. However, resorption in the mandible periosteum envelope is associated with cholinergic Vasoactive Intestinal Peptide (VIP)-positive nerve fibers sensitive to sympathetic neurotoxics, suggesting that different sympathetic pathways may control distinct bone envelopes. In this study, we assessed the role of distinct sympathetic pathways on rat femur and mandible envelopes. To this goal, adult male Wistar rats were chemically sympathectomized or treated with agonists/antagonists of the catecholaminergic and cholinergic pathways; femora and mandibles were sampled. Histomorphometric analysis showed that sympathectomy decreased the number of preosteoclasts and RANKL-expressing osteoblasts in mandible periosteum but had no effect on femur trabecular bone. In contrast, pharmacological stimulation or repression of the catecholaminergic cell receptors impacted the femur trabecular bone and mandible endosteal retromolar zone. VIP treatment of sympathectomized rats rescued the disturbances of the mandible periosteum and alveolar wall whereas the cholinergic pathway had no effect on the catecholaminergic-dependent envelopes. We also found that VIP receptor-1 was weakly expressed in periosteal osteoblasts in the mandible and was increased by VIP treatment, whereas osteoblasts of the retromolar envelope that was innervated only by tyrosine hydroxylase-immunoreactive fibers, constitutively expressed beta-2 adrenergic receptors. These data highlight the complexity of the sympathetic control of bone metabolism. Both the embryological origin of the bone (endochondral for the femur, membranous for the mandibular periosteum and the socket wall) and environmental factors specific to the innervated envelope may influence the phenotype of the sympathetic innervation. We suggest that an origin-dependent imprint of bone cells through osteoblast-nerve interactions determines the type of autonomous system innervating a particular bone envelope.