Microbiota is increasingly being recognized as an important factor in human health. Alterations in the bacterial community structure have been implicated in a wide range of human diseases. Most therapeutic strategies targeting microbiota, such as probiotics, prebiotics and fecal transplantation, aim to modulate the bacterial community. Herein we demonstrate that the cell free bacterial DNAs (cfbDNAs) are extensively observed in human bloodstreams and gradually arise along with growth. Moreover, patients with immune-related diseases, e.g. inflammatory bowel disease (IBD), kawasaki disease (KD) and HIV, own higher amounts of cfbDNAs with lower microbial biodiversity compared with healthy individuals by using real-time PCR measurement and high-throughput 16S rDNA sequences analyses. Further comparisons reveal that 173 genera exhibit preferential abundance in either healthy individuals or patients, providing “molecular phenotypes” of the corresponding diseases in a manner of microbiome, especially in those IBD patients post/pre-therapy. Although the origination and function of these cfbDNAs in human circulating bloodstreams remain unclear, their taxonomic variations offer fingerprints for potential applications in noninvasive and safe pre-diagnosis or prognosis, and provide clues for further understanding of the host-microbiota interactions.