Abstract
Background and Objectives: There is an increasing focus on the effect of the gut microbiome on developing atherosclerosis, but there is still no unified standpoint. We aimed to find associations between intestinal microbiome diversity and a marker of subclinical atherosclerosis, the carotid intima-media thickness (IMT). Materials and Methods: Recruited from the Hungarian Twin Registry, 108 monozygotic (MZ) twins (mean age 52.4 ± 14.1 years, 58% female) underwent a comprehensive carotid ultrasound examination (Samsung RS85). Of the 108 MZ twins, 14 pairs (mean age 65 ± 6.4 years, 71% female) discordant for carotid IMT were selected to undergo a stool sample collection. A special stool sampling container was mailed and received from each participant. After DNA extraction, library construction was performed specifically for the V3–V4 hypervariable region of microbial 16S rRNA. Next, the microbiome composition of the samples was determined using Kraken software. Two hypotheses were tested with the exact permutation test: (1) in the group with normal IMT, the Shannon index of the phyla is higher; and (2) the Firmicutes/Bacteroidetes ratio is greater in the group with high IMT values. Furthermore, the abundance of different bacterial strains present at higher and normal IMT was also explored. Statistical analysis was carried out using R software. Results: Increased Firmicutes/Bacteroidetes ratio was associated with increased IMT (mean Firmicutes/Bacteroidetes ratio of IMT > 0.9 and IMT < 0.9 groups: 2.299 and 1.436, respectively; p = 0.031). In the group with normal IMT values, a substantially higher fraction of Prevotellaceae was observed in contrast with subjects having subclinical atherosclerosis. However, there was no significant difference in the alpha diversity between the two groups. Conclusions: The determining role of individual genera and their proportions in the development and progression of atherosclerosis can be assumed. Further studies are needed to clarify if these findings can be used as potential therapeutic targets.
Highlights
Carotid artery atherosclerosis (CAS) is known to be associated with increased risk for cardiovascular diseases (CVDs) [1,2,3], which are the leading causes of death globally, taking an estimated nearly 18 million lives each year [4]
Segment-specific genetic influence of carotid intima-media thickness (IMT) was studied in a large Korean twin population, which reported moderately high heritability of 0.48 for common, 0.38 for carotid bifurcation, and 0.45 for internal carotid artery [6]
Well-known cardiovascular risk factors associated with carotid IMT, influencing specific segments of the carotid artery, are, for men, alcohol consumption, physical activity (common carotid artery (CCA) and internal carotid artery (ICA)), body mass index (BMI), diabetes, hypertension (ICA), and highdensity lipoprotein (HDL) cholesterol (CCA and bifurcation); on the other hand, for women, they are smoking, hypertension (CCA), total and low-density lipoprotein (LDL) cholesterol, and high-sensitivity Creactive protein (CCA and ICA) [6]
Summary
Carotid artery atherosclerosis (CAS) is known to be associated with increased risk for cardiovascular diseases (CVDs) [1,2,3], which are the leading causes of death globally, taking an estimated nearly 18 million lives each year [4]. Well-known cardiovascular risk factors associated with carotid IMT, influencing specific segments of the carotid artery, are, for men, alcohol consumption (bifurcation), physical activity (common carotid artery (CCA) and internal carotid artery (ICA)), body mass index (BMI) (all segments), diabetes (bifurcation and ICA), hypertension (ICA), and HDL cholesterol (CCA and bifurcation); on the other hand, for women, they are smoking (bifurcation), hypertension (CCA), total and low-density lipoprotein (LDL) cholesterol (bifurcation and ICA), and high-sensitivity Creactive protein (hs-CRP) (CCA and ICA) [6]. These findings explain the differences in the incidence of cardiovascular disease between men and women.
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