Abstract

Objective: The gut microbiota of patients with coronary artery disease is being shown to differ from that of healthy individuals. However, it is unclear whether it is altered before the onset of the disease. The aim of this study is to investigate the association between gut microbiota and subclinical coronary artery calcification (CAC) in general Japanese men. Design and method: We randomly selected men from the general Japanese population, who underwent computed tomography and gut microbiology tests between 2010 and 2016. Among participants who underwent both tests, excluding those with myocardial infarction history, leaving a sample size of 653 participants in the analysis. DNA was extracted from fecal samples, the bacterial 16S ribosomal RNA gene was amplified using a two-step tail polymerase chain reaction method, and DNA sequencing was performed on a MiSeq System, followed by data analysis using QIIME2 algorithm. Agatston scores > = 100 was defined as the presence of CAC. LEfSe identified different taxa between with and without CAC, and Poisson regression analysis examined them when logarithmic LDA score was > = 3.5 and phylogenetic levels > = 3. Each taxon was ranked in quartiles (Q1–4) and the relative risk (RR) of CAC was calculated. Adjustment factors were age, smoking, drinking, body mass index, use of medication to treat hypertension, dyslipidemia, or diabetes, and history of cardiovascular events. Sensitivity analysis also delimited Agatston scores by 0 or 10. Results: Mean age of the participants was 68.3 years, and 215 (32.9%) participants had a CAC score > = 100. Relative abundance of phylum level was 55.1% and 53.2% for Firmicutes, and 32.4% and 34.3% for Bacteroidetes among participants with versus without CAC score > = 100, respectively. Among taxa identified by LEfSe, Poisson regression analysis revealed the genus Bacteroides was inversely associated and genus Ruminococcus was positively associated with CAC after multivariable adjustment (Bacteroides: RR [95%CI] = 0.62 [0.45–0.86] (Q4) vs. ref (Q1)) (Ruminococcus: RR [95%CI] = 1.69 [1.25–2.29] (Q4) vs. ref (Q1)). Sensitivity analysis showed similar results. Conclusions: The ratio of Firmicutes to Bacteroidetes was high from the beginning of atherosclerosis. Higher genus Ruminococcus and lower genus Bacteroides were associated with a CAC score > = 100 in general Japanese men.

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