Circulating Microbial Cell-Free DNA in Health and Disease

Abstract

Human blood contains low biomass of circulating microbial cell-free DNA (cfmDNA) that predominantly originates from bacteria. Numerous studies have detected circulating cfmDNA in patients with infectious and non-infectious diseases, and in healthy individuals. Remarkable differences were found in the microbial composition of healthy subjects and patients compared to cohorts with various diseases or even patients with diversified prognoses, implying that these alterations may be associated with disease development. Although the function of circulating cfmDNA needs to be elucidated (whether it acts as a bystander of dysbiosis or a key player in disease development), several studies have demonstrated its potential as a non-invasive biomarker that may improve diagnosis and treatment efficacy. The origin of circulating cfmDNA is still the subject of much deliberation, but studies have identified members of various microbiome niches, including the gut, oral cavity, airways, and skin. Further studies investigating the origin and function of circulating cfmDNA are needed. Moreover, low-biomass microbiome studies are prone to contamination, therefore stringent negative experimental control reactions and decontamination frameworks are advised in order to detect genuine circulating cfmDNA.

A new method using rapid Nanopore metagenomic cell-free DNA sequencing to diagnose bloodstream infections: a prospective observational study

“…Validation and interpretation of mNGS results in patients with a negative blood culture is difficult and the many additional findings have led to questions on the clinical relevance of these identifications. 27,28 In the BSI-suspected group from this study, the high number of microbiological tests from other sites that confirm the mNGS result and the fact that patients were included in this group upon suspicion of a systemic infection, supports the relevance of mNGS pathogen identifications. Further, no microbes were identified with mNGS in patients from the BSI-absent group.…”

Visualization of the individual blood microbiome to study the etiology of sarcoidosis

“…The presence of over 95% of human DNA in the samples may mask the microbial content during the library amplification steps despite treatment with DNase I and washing steps included in the protocol prior to microbial DNA extraction (Materials and Methods). The amount of the microbial DNA in blood was estimated to be less than 0.2% [62] . The study’s main limitation was the potential depletion of microbial DNA by human DNA.…”

Infective Endocarditis during Pregnancy—Keep It Safe and Simple!

“…Cell-free deoxyribonucleic acid (DNA) next-generation sequencing is a useful diagnostic tool, superior to the methods presented above because of the longer time interval in which it can identify the pathogen compared to standard blood cultures [ 81 , 82 , 83 ]. Circulating cell-free DNA was first discovered in 1948 by Mandel et al [ 84 , 85 ]. Blood contains small amounts of it, predominantly from bacteria, and is a veritable reservoir of genetic material from all the body’s cells [ 86 , 87 ].…”