Abstract
Gut dysbiosis, alongside a high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiomes of 15 age-matched CAD patients and healthy controls were analyzed by 16S rRNA sequencing analysis. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients’ sera on endothelial cells was investigated. 16S rRNA sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated LPS and indoxyl sulfate levels in patients’ sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production. Moreover, both of these metabolites promoted thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression.
Highlights
Bacterial metabolites leaking from the gut into the bloodstream can affect the vascular endothelium directly or indirectly by factors released from white blood cells upon contact with bacterial antigens
The 16S ribosomal RNA (rRNA) analysis revealed noteworthy differences in gut microbiome composition at the phylum, class, order, family, and genus levels in coronary arterial disease (CAD) patients compared to a group of healthy subjects (Figures 1 and 2)
The most striking difference was Bacteroidetes depletion in CAD patients compared to HC (p = 0.01)
Summary
Coronary artery disease (CAD) includes stable and unstable angina, myocardial infarction, and sudden cardiac death, the primary cause of morbidity and mortality worldwide [1]. Gut dysbiosis related to the change in diversity and abundance of resident intestinal microbiota plays a vital role in cardiovascular diseases [2,3]. Gut dysbiosis induces chronic inflammation resulting in increased intestinal epithelial permeability and leakage of bacterial metabolites into the bloodstream [4]. Some of these metabolites can activate endothelial cells and promote atherosclerosis. Bacterial metabolites may interact with each other increasing their mutual cytotoxicity to the endothelial cells directly or indirectly via the effect on monocyte/macrophage
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