Tracing the Origins of Microbial DNA in Human Blood via Comparative Metagenomic Profiling
Cell-free DNA (cfDNA) in human blood is a valuable non-invasive biomarker, particularly through circulating tumor DNA (ctDNA) for cancer detection. Microbial DNA fragments have also been detected in blood, but their origin and clinical significance remain unclear. In this study, we investigated the source of circulating microbial DNA by comparing blood samples from healthy individuals and patients with colorectal cancer or inflammatory bowel disease (IBD) to reference microbiome datasets representing various body sites, including the skin, gut, vagina, oral cavity, and nasal cavity. We applied a comprehensive metagenomic analysis pipeline, incorporating diversity metrics and microbial source tracking models (SourceTracker, FEAST, SourceID-NMF), to estimate the relative contributions of different anatomical sites to the blood microbial DNA. Our findings reveal strong compositional similarities between blood and skin/nasal microbiomes, with notable variation associated with disease status. These results improve our understanding of blood microbial DNA and its potential utility in non-invasive diagnostics.