title: 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.
authors.affiliation: Department of Genetics, Center for excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamilnadu, India.
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Dinakaran
authors.affiliation: Department of Cardiothoracic Surgery, Madurai Medical College & Government Rajaji Hospital, Madurai, Tamilnadu, India.
authors.forename: Andiappan
authors.initials: A
authors.lastname: Rathinavel
authors.affiliation: Department of Genetics, Center for excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamilnadu, India.
authors.forename: Muthuirulan
authors.initials: M
authors.lastname: Pushpanathan
authors.affiliation: Department of Genetics, Center for excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamilnadu, India.
authors.forename: Ramamoorthy
authors.initials: R
authors.lastname: Sivakumar
authors.affiliation: Department of Genetics, Center for excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamilnadu, India.
authors.forename: Paramasamy
authors.initials: P
authors.lastname: Gunasekaran
authors.affiliation: Department of Genetics, Center for excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamilnadu, India.
authors.forename: Jeyaprakash
authors.initials: J
authors.lastname: Rajendhran
mesh_terms: D039903:Actinobacteria / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002318:Cardiovascular Diseases / Q000097:blood* / Q000382:microbiology / Q000821:virology; D004247:DNA / Q000097:blood*; D004269:DNA, Bacterial / Q000097:blood / Q000235:genetics; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D056186:Metagenomics; D008875:Middle Aged; D011424:Propionibacterium / Q000235:genetics; D020560:Proteobacteria / Q000235:genetics; D017105:Pseudomonas Phages / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000097:blood / Q000235:genetics; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D004279:DNA, Viral; D012336:RNA, Ribosomal, 16S; D055544:beta-Globins; D004247:DNA