Study Finds No Evidence for Common Blood Microbiome

There does not appear to be a common blood microbiome, despite research in recent years suggesting the possibility, according to the findings of a new study. Investigators in Singapore examined DNA signatures of microbes in the blood of nearly 10,000 healthy individuals but found that most (84%) had no microbial DNA in their blood samples, concluding that the presence of microbes is infrequent and sporadic.

“If we take the definition of a ‘microbiome’ as a microbial community whose member species interact among themselves and with their ecological niche, we found no consistent circulating blood microbiome in healthy individuals,” the researchers wrote in a research briefing in Nature Microbiology published online on March 30.

A handful of studies in recent years — both culture-based and culture-independent approaches — have suggested the presence of multiple microbial species in blood, raising the possibility of a common blood microbiome, such as those found in other body systems like the gut. However, these studies have involved relatively small cohorts or lacked the ability to rule out contamination. Blood has traditionally been viewed as a sterile environment with transient microbial species present that raise the risk of morbidity and mortality in individuals with compromised immune systems, such as following surgery.

In this study, the researchers determined that microbial DNA detected in healthy blood cultures was associated with “sporadic translocation” of DNA from commensal organisms from other locations in the body. Of the 117 species identified, the most prevalent was Cutibacterium acnes, (4.7%) — a gram-positive bacterium linked to the skin condition of acne — which suggested that none of the identified microbes were ‘core’ to a blood microbiome.

The 18% of individuals with detected microbial DNA had a median of one species. The researchers believe that the DNA sequencing performed was robust enough to identify more bacterial DNA had it been present and to distinguish between contaminants and DNA genuinely present in the sample.

The researchers specified that “the ‘microbiome’ should refer to a community of microbes that interact with each other and with the environment in their ecological niche. Therefore, in a blood microbiome, microbes should exhibit community structures indicated by co-occurrence or mutual exclusion of species.” They did not find evidence of co-occurrence of species in multiple samples.

In addition, the microbial species identified in the blood of healthy individuals was distinct from those identified in 11 years of hospital blood culture records.

In order to verify that they were not identifying free DNA in the blood from contaminants, the researchers looked for indications of replicating bacteria. Out of 20 species with enough data for analysis, investigators found 11 with evidence of replication. In addition, only one of the identified species with replicating ability is present in hospital blood culture records.

This study is believed to be the largest-scale analysis so far of microbial signatures in human blood, noting that “the bloodstream allows microbes to move between different body sites in healthy individuals. However, the low prevalence of the detected species suggests that this movement is likely to be infrequent and transient.”

The researchers concluded that the study lays the groundwork for research to answer key remaining questions regarding the degree of interconnected of microbiomes at various body sites, whether these processes are altered during disease, and whether changes to the microbial community at one body site can alter those at another site. Lastly, it will be important to determine how the body’s immune system regulates microbes in the blood.