New Study Finds 99% of Microbes in Human Body Previously Unknown

A new study published in the Proceedings of the National Academy of Sciences determined that our bodies are host to a number of diverse microbes that were previously unidentified.

This work was led by principal investigator, Stephen Quake, PhD, professor of bioengineering and applied physics at Stanford University. Professor Quake and his colleagues utilized shotgun sequencing and examined circulating cell-free DNA (cfDNA) from patient blood to determine the microbiome landscape. The study included 188 patients in 4 cohorts: heart transplant (76 patients, 610 samples), lung transplant (59 patients, 460 samples), bone marrow transplant (21 patients, 161 samples), and pregnancy (32 patients, 120 samples).

The authors sequenced 37 billion molecules from the cfDNA sample and found that 0.45% of the reads were non-human. Intriguingly, the authors aligned these non-human reads to known microbes in a database that consists of 8000 species of bacteria, viruses, fungi, and other organisms and found that only 1% of these reads belonged to known microorganisms. In other words, a staggering 99% of the non-human reads correspond to previously unidentified species. In an effort to find out more about these unknown species, the authors performed de novo assembly on the non-human reads using an iterative approach, making sure to screen for contaminants and artifacts.

Professor Quake and his colleagues found that approximately two-thirds of the sequences belong to bacterial species and are most similar to the phylum Proteobacteria, which include species like Escherichia coli and Vibrio cholerae. In addition, 9% of the sequences are of viral origin, the majority of which are either phages or torque teno viruses (TTVs), which include the family of anelloviruses. The TTVs identified seem to cluster around immunocompromised patients, which validates what had been previously shown in the literature. Overall, the authors determined that they observed more than 1000 new taxa and have doubled the number of anelloviruses known to be found in humans.

This study sheds light on the wealth of microbial diversity found in the human body, which had been previously underestimated. Although previous work has utilized a similar approach, earlier studies examined specific organs such as the skin or the gut. The drawback of such an approach is that organisms present in other niches or in low abundances are not detected. By examining blood, which should contain samples from the entire body, the authors were able to characterize the human microbiome in multiple patient populations in a comprehensive and unbiased manner. Professor Quake is quoted in a press release saying, “We found things that are related to things people have seen before, we found things that are divergent, and we found things that are completely novel.”

The results are powerful as they provide information on previously unidentified organisms, which has the potential to revolutionize the field of infectious disease and open doors for new therapeutics. Professor Quake remarked on one of the implications of the study, stating, "What this does is it arms infectious disease doctors with a whole set of new bugs to track and see if they're associated with disease.”

Samar Mahmoud graduated from Drew University in 2011 with a BA in Biochemistry and Molecular Biology. After two years of working in the industry as a Quality Control Technician for a blood bank, she went back to school and graduated from Montclair State University in 2016 with an MS in Pharmaceutical Biochemistry. She is currently pursuing her PhD in Molecular and Cellular Biology at the University of Massachusetts at Amherst.