Oral Microbiome in Carotid Atherosclerosis

Official title

The Role of the Oral Microbiome in Carotid Atherosclerosis: Investigating in a Cross-sectional Study the Microbial Influence on Plaque Development and Vulnerability Based on Biobank Data

Overview

The goal of this observational study, called OMICA (Oral Microbiome in Carotid Atherosclerosis), is to learn how bacteria living in the mouth may influence the development and stability of plaques in the carotid arteries, which supply blood to the brain. Plaque buildup in these arteries can lead to stroke. Researchers want to understand whether certain oral bacteria are linked to plaque vulnerability, meaning a higher chance that the plaque will rupture and cause a stroke. The study will include a cohort of adults scheduled for carotid endarterectomy at Semmelweis University. Participants will be enrolled in the Semmelweis University Carotid Biobank project. The main questions the study aims to answer are: Do people with more severe gum disease or tooth infection have a higher number of bacteria in their carotid plaques, and are those plaques more likely to rupture? Are the bacteria found in vulnerable plaques different from those in stable plaques? Are similar bacteria found in the mouth, gut, and plaques, suggesting that bacteria may travel through the body? What participants will do: Have their oral health checked before surgery, including an exam of gum disease and tooth infections. Provide microbiome samples from the mouth, anus, urine, and carotid plaque (taken during surgery). Have preoperative photon-counting computed tomography (CT) performed to assess plaque stability and study eligibility. All samples and imaging data will be analyzed to identify bacterial species and their relationship to plaque type. The study does not involve any experimental treatment or medication. Participation adds no significant medical risk beyond standard care. Researchers will compare bacterial patterns between people with vulnerable plaques and those with stable plaques to identify microbial signatures linked to carotid plaque instability. The results may help create future microbiome-based risk models for detecting people at higher risk of stroke or severe atherosclerosis.

Detailed description

Background and Rationale: Cardiovascular diseases are currently the leading cause of death globally, according to the World Health Organization. Recent studies report a 4.2% prevalence of moderate to severe carotid artery stenosis. A growing body of evidence highlights the association between poor oral health and vascular disease. Periodontitis is a highly prevalent condition, affecting approximately 10% of the global population with its severe form (1). Several studies have revealed correlations between the severity of periodontal disease and the presence of pathogenic bacteria in carotid (2) and atherosclerotic plaques (3).

Methods:

Population: The cross-sectional study includes a cohort of patients undergoing carotid endarterectomy: roughly half with vulnerable and half with stable carotid plaques. Photon-counting computed tomography (CTA) is part of the preoperative eligibility assessment confirming internal carotid artery stenosis and determining inclusion in the study. Only non-invasive magnetic resonance (MR) and ultrasound imaging will be requested from participants as part of the study protocol for classification of plaque vulnerability. All imaging data will be anonymized in accordance with Semmelweis University data protection protocols.

Intervention (Sample Collection): This study involves preoperative oral health evaluation and the collection of oral, anal, urine, blood, and carotid plaque samples during carotid endarterectomy for microbiome analysis. All samples and corresponding data will be fully anonymized and processed within the Semmelweis University Carotid Plaque Biobank (BM/33955-1/2023).

Comparator: Patients with vulnerable vs. stable carotid plaques, as classified by carotid duplex ultrasound (GSM score) and photon-counting CTA and MR plaque characterization.

Outcome:

1. Identification of periodontal and endodontic pathogens in the oral microbiome that positively correlate with plaque severity and vulnerability. 2. Distinct microbiome compositions in carotid plaques of patients with stable versus vulnerable lesions, supporting the role of bacterial colonization in plaque instability. 3. Detection of microbiome similarities across oral, anal, and vascular samples, suggesting systemic bacterial dissemination that may contribute to carotid stenosis progression.

Expected Value of Results: This project integrates microbiome and imaging data to explore links between oral bacteria and carotid plaque vulnerability. By investigating the interplay between oral microbiota and vascular disease, the study aims to deepen our understanding of plaque pathogenesis and progression. The findings may contribute to developing microbiome-based risk prediction models for plaque vulnerability, supported by advanced imaging data.

Interventions

• Other Sample Collection
  Participants undergo preoperative oral health evaluation and the collection of oral, anal, urine, blood, and carotid plaque samples during carotid endarterectomy for microbiome analysis. All samples are fully anonymized and processed within the Semmelweis University Carotid Plaque Biobank (BM/33955-1/2023). No experimental treatments are administered; all activities occur within the framework of biobank-approved surgical and diagnostic procedures.

Primary outcome measures

• Identification of Oral and Carotid Plaque Microbiome Associations [Time frame: At time of carotid endarterectomy]

Secondary outcome measures (2)

• Differences in Microbiome Composition Between Vulnerable and Stable Carotid Plaques [Time frame: At time of carotid endarterectomy]
• Identification of Shared Microbial Taxa Across Oral, Anal, Urine, and Carotid Plaque Samples [Time frame: At time of carotid endarterectomy]

Eligibility criteria

Inclusion criteria

• Confirmed internal carotid artery (ICA) stenosis on preoperative photon-counting computed tomography (CTA)
• Adults (≥18 years) undergoing carotid endarterectomy at Semmelweis University.
• Eligible for surgery based on standard anesthesiologic evaluation.
• Willing and able to provide written informed consent for participation and sample collection.

Exclusion criteria

• Active systemic infection or current antibiotic therapy within 30 days before surgery.
• Immunosuppressive therapy or immunodeficiency disorders.
• Inability to undergo MRI (e.g., pacemaker, metallic implants, severe claustrophobia).
• Pregnancy or lactation.
• Malignancy under active treatment.
• Prior carotid surgery or stenting on the same side.
• Refusal or inability to provide informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Hungary · 1 center

• Városmajor Heart and Vascular Center, Semmelweis University — Budapest

Publications

• Isoshima D, Yamashiro K, Matsunaga K, Taniguchi M, Matsubara T, Tomida S, Ota S, Sato M, Shimoe Y, Kohriyama T, Arias Z, Omori K, Yamamoto T, Takashiba S. Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis. Odontology. 2021 Jan;109(1):239-249. doi: 10.1007/s10266-020-00524-w. Epub 2020 May 19. PMID 32430725
• Brun A, Nuzzo A, Prouvost B, Diallo D, Hamdan S, Meseguer E, Guidoux C, Lavallee P, Amarenco P, Leseche G, Bouchard P, Michel JB, Range H. Oral microbiota and atherothrombotic carotid plaque vulnerability in periodontitis patients. A cross-sectional study. J Periodontal Res. 2021 Apr;56(2):339-350. doi: 10.1111/jre.12826. Epub 2020 Dec 25. PMID 33368263
• Frencken JE, Sharma P, Stenhouse L, Green D, Laverty D, Dietrich T. Global epidemiology of dental caries and severe periodontitis - a comprehensive review. J Clin Periodontol. 2017 Mar;44 Suppl 18:S94-S105. doi: 10.1111/jcpe.12677. PMID 28266116

Identifiers

NCT: NCT07296965 · NKFI-Advanced 149634 · NKFI-Advanced 149634 · BM/33955-1/2023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗