Oral microbiome diversity associates with carotid intima media thickness in middle-aged male subjects

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Reviewed Marked as Reviewed by Svetlana up on 2025-4-10
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Akhi R, Lavrinienko A, Hakula M, Tjäderhane L, Hindström R, Nissinen A, Wang C, Auvinen J, Kullaa AM, Ylöstalo P, Salo T, Kaikkonen K, Koskimäki JJ, Hörkkö S
Journal
Communications medicine
Year
2025
BACKGROUND: Although there have been significant advancements in reducing the burden of cardiovascular disease (CVD) by modifying traditional CVD risk factors, substantial risks persist, particularly among male subjects who exhibit heightened susceptibility to atherosclerosis. In this context, we aim to study the link between oral microbiome and carotid intima media thickness (cIMT). METHODS: The Northern Finland Birth Cohort of 1966 (mean age 46 years, n = 869) underwent an extensive health examination, including the measurement of cIMT. The oral microbiome was also investigated using high-throughput 16S rRNA gene sequencing. RESULTS: Here we show that oral microbiome diversity links with atherosclerosis risk factors, namely smoking, glycemic balance, low-grade inflammation, and periodontitis. After excluding CVD-influencing factors (n = 339), oral microbiome genera (p = 0.030), Shannon index (p = 0.001), β-diversity Bray-Curtis (p < 0.001), and Jaccard (p < 0.001) are associated with cIMT in males, but not in the female sub-cohort. Furthermore, in the male sub-cohort (n = 131), the genera Prevotella, Megasphaera, and Veillonella associate positively with cIMT, while Absconditabacteria, Capnocytophaga, Gemella, Fusobacterium, Neisseria, Aggregatibacter, Tannerella, Treponema, Cardiobacterium, and Bacteroidales associate inversely with cIMT. We examine the involvement of serum total immunoglobulins and antibodies to phosphorylcholine (PCho) and malondialdehyde-acetaldehyde LDL (MAA-LDL) with cIMT. Subjects with high cIMT have lower levels of serum total IgA (p = 0.009), IgA to PCho (p = 0.017), and IgG to PCho (p = 0.008). The relative abundance of cIMT-associated genera correlates with serum IgA antibodies. CONCLUSIONS: This middle-aged birth cohort study shows that male oral microbiome diversity links to cIMT, suggesting a potential sex-specific interaction between the oral microbiome and atherosclerosis. Heart disease remains a leading cause of death worldwide and particularly affects men. In this study, we explored whether bacteria in the mouth are associated with artery thickness, a key early indicator of heart disease. We analyzed data from 869 participants, all approximately 46 years old, from the Northern Finland Birth Cohort. Among men, we found that certain groups of bacteria in the mouth were linked to increased artery thickness, a connection not observed in women. These findings suggest that the composition of bacteria in the mouth may influence heart disease risk, especially in men. Understanding this connection could lead to new heart disease prevention strategies.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/07

Curator: Montana-D

Revision editor(s): Montana-D, KateRasheed

Subjects

Location of subjects
Finland
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Carotid artery intima media thickness Carotid artery intima media thickness,carotid artery intima media thickness
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Inverse association with male cIMT (carotid Intima Media Thickness)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Positive association with male cIMT (carotid Intima Media Thickness)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Subjects with Positive association with male cIMT (carotid Intima Media Thickness)

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Linear Regression
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
blood pressure, body mass index, Confounders controlled for: "LDL (low-density lipoprotein)" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.LDL (low-density lipoprotein)


Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/07

Curator: Montana-D

Revision editor(s): Montana-D

Source: Figure 2B

Description: The association of males with low cIMT and high cIMT with statistically significant oral bacteria taxa

Abundance in Group 1: increased abundance in Positive association with male cIMT (carotid Intima Media Thickness)

NCBI Quality ControlLinks
Prevotella
Megasphaera
Veillonella

Revision editor(s): Montana-D

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-10

Curated date: 2025/04/07

Curator: Montana-D

Revision editor(s): Montana-D

Source: Figure 2B

Description: The association of males with low cIMT and high CIMT with statistically significant oral bacteria taxa.

Abundance in Group 1: decreased abundance in Positive association with male cIMT (carotid Intima Media Thickness)

NCBI Quality ControlLinks
Candidatus Absconditibacteriota
Capnocytophaga
Gemella
Fusobacterium
Neisseria
Aggregatibacter
Tannerella
Treponema
Cardiobacterium
Bacteroidales

Revision editor(s): Montana-D