Elevated Levels of Circulating DNA in Cardiovascular Disease Patients: Metagenomic Profiling of Microbiome in the Circulation

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. An expanding body of evidence supports the role of human microbiome in the establishment of CVDs and, this has gained much attention recently. This work was aimed to study the circulating human microbiome in CVD patients and healthy subjects. The levels of circulating cell free DNA (circDNA) was higher in CVD patients (n = 80) than in healthy controls (n = 40). More specifically, the relative levels of circulating bacterial DNA and the ratio of 16S rRNA/β-globin gene copy numbers were higher in the circulation of CVD patients than healthy individuals. In addition, we found a higher circulating microbial diversity in CVD patients (n = 3) in comparison to healthy individuals (n = 3) by deep shotgun sequencing. At the phylum level, we observed a dominance of Actinobacteria in CVD patients, followed by Proteobacteria, in contrast to that in healthy controls, where Proteobacteria was predominantly enriched, followed by Actinobacteria. The circulating virome in CVD patients was enriched with bacteriophages with a preponderance of Propionibacterium phages, followed by Pseudomonas phages and Rhizobium phages in contrast to that in healthy individuals, where a relatively greater abundance of eukaryotic viruses dominated by Lymphocystis virus (LCV) and Torque Teno viruses (TTV) was observed. Thus, the release of bacterial and viral DNA elements in the circulation could play a major role leading to elevated circDNA levels in CVD patients. The increased circDNA levels could be either the cause or consequence of CVD incidence, which needs to be explored further.

Endotoxin Effects on Cardiac and Renal Functions and Cardiorenal Syndromes

“…Dinakaran et al [86] have observed elevated concentrations of bacterial DNA in patients with heart disease compared to healthy subjects, and even bacteria composition was found to differ between the groups. The intricate interaction between the heart and the gut has recently emerged as an innovative concept to provide new insights in the setting of HF.…”

New Aspects on the Metabolic role of Intestinal Microbiota in the Development of Atherosclerosis

“…Indeed, there is evidence that an impaired balance of gut microbiota is associated, for example, with inflammatory bowel disease [3]. On the other hand, the use of probiotics or synbiotics A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 4 may lead to transient endotoxemia and cell-free DNA circulating in the blood, both conditions being associated with cardiovascular disease [9][10][11].…”

Rapid Detection of Cell-Free Mycobacterium tuberculosis DNA in Tuberculous Pleural Effusion

“…It is well-known that cell-free tumor cell DNA and fetal cfDNA can be detected in various body fluids, such as plasma, urine, and PE (18)(19)(20). Recently, the detection of cfDNA from pathogens, including fungi, bacteria, and parasites, has been reported (21)(22)(23). A nucleic acid amplification test (NAAT) detecting cfDNA from the pathogen has shown better sensitivity than just the detection of genomic DNA from the same pathogen.…”