Distinct composition and functions of circulating microbial DNA in peripheral blood and fecal microbiome of healthy individuals

The crucial role of circulating microbial DNA (cmDNA) in peripheral blood is gaining recognition for its importance in normal physiology and immunity in healthy individuals. Originating from strongly colonizing gut microbes, recent evidence suggests that cmDNA in peripheral blood is derived from these translocating microbes, although its association with and differences from the gut microbiome remain unclear. We collected blood, urine, and fecal samples from the same volunteers to compare their microbial information by 16S rDNA sequencing. Our study revealed that cmDNA in peripheral blood indicates reduced diversity and distinct flora composition compared to the gut microbiome, with dominant species and an increased abundance of disease-related DNA. Interestingly, cmDNA in blood showed a limited presence of DNA from anaerobes and gram-positive bacteria, in contrast with the trend observed in fecal samples. Furthermore, analysis of cmDNA revealed traits associated with mobile elements, biofilm formation, and potential pathological and stress tolerance, among others, which were minimal in stool samples. Notably, the microbial functions and phenotypes of blood and urine samples after cmDNA analysis were similar, albeit with higher diversity observed in urine samples. Source Tracker analysis of blood cmDNA origin further indicated that gut microbes may not be the primary source or that a selective screening mechanism exists, allowing specific microbial DNA populations to enter peripheral blood. In conclusion, our study highlights the unique composition and potential functions of cmDNA in peripheral blood, emphasizing its selective presence and requiring further research to elucidate the underlying mechanisms.