Last post I described fascinating research on the immune response by the Mark Davis Lab at Stanford. But another Stanford research team, led by Steven Quake, has published the results an equally exciting study. In fact, the team’s discovery marks one of the most important findings in modern science.
Quake and team used new methods to search for the DNA of microbes in human blood and tissue. They found that 99% of microbes identified were previously unknown to science. As this article in Stanford News describes, the discovery clarifies that “the microbes living within us are vastly more diverse than previously known.”
To be specific, Quake and team examined microbe DNA fragments in the blood of patients with a range of conditions characterized by immunosuppression (liver transplant recipients, pregnant women etc). They collected over 1,000 blood samples, and found that they contained hundreds of never before discovered bacteria and viruses. In fact, ~3,761 of the organisms detected represent microbes not known to exist before the study was performed.
These species include thousands of new bacteria, but also new viruses and phages (viruses that infect bacteria). The research team was forced to add new branches to the “tree of life” in order to classify many of these new microbes. Indeed, their findings literally double the total number of anelloviruses found in humans.
Quake and team conclude their paper by stating that these novel microbes “have potential consequences for human health. They may prove to be the cause of acute or chronic diseases that, to date, have unknown etiology…”
More thoughts: I experienced several “eureka moments” while reading the Quake study. First, I have long predicted that new microbes would be identified in human tissue and blood. I began my microbiology career by studying the work of microbiologists/pathologists in the 1960s. The papers/textbooks published by these scientists are seldom discussed in 2017. However, their work repeatedly identified numerous microbes/pathogens in blood/tissue samples taken from human subjects.
Why are these 1960s studies seldom referenced? In the 1970s, the “theory of autoimmunity” gained hold and research on chronic microbes was largely shelved. When the 1960s microbiologists contested this mindset, their work was often dismissed on the basis of contamination (they were told that external microbes in their laboratories had “contaminated” their human samples). I’ve never believed these claims to be accurate, but most of the general scientific community has accepted them.
In fact, the possible contamination of blood/tissue samples by laboratory microbes is an ongoing concern: Quake and team were careful to include a full section in their paper called “Novel Contigs (DNA reads) are Not Artifacts or Contaminants.” There, they discuss the results of several extra experiments aimed at proving exactly that (see the study’s Methods section).
Furthermore, over the past two decades, several research teams using molecular tools have already identified numerous microbes in the blood. For example, this 2001 study by Stanford researcher Dave Relman found many bacterial species in the blood of healthy subjects. Relman is one of my greatest role models, so I’ve taken his findings and related studies very seriously.
The Quake study also hammers home a point I’ve made in every speech/paper/book chapter since 2005. Imbalances of the gut microbiome, and external body microbiomes (skin, mouth etc) can contribute to chronic disease. However, microbes in the blood reach internal human tissue, and thus may play the greatest role in driving infectious disease processes. This is especially true since many of these blood/tissue microbes persist inside the cells of the immune system. Quake and team echo this sentiment in their paper stating, “Blood circulates throughout the human body and contains molecules drawn from virtually every body tissue.” Quake also told Stanford News the following about his team’s discovery:
“I’d say it’s not that baffling in some respects because the lens that people examined the microbial universe was one that was very biased…For one thing, researchers tend to go deep in the microbiome in only one part of the body, such as the gut or skin, at a time. Blood samples, in contrast, “go deeply everywhere at the same time.”
Last but not least, the Quake team derived their results by correctly separating the microbe DNA in their samples from the human DNA in their samples. This distinction can prove difficult because microbe and human DNA are often very similar in structure.
Many other research teams studying the microbiome ARE NOT DOING THIS (CORRECTLY SEPARATING MICROBE/HUMAN DNA). In conjunction with my colleague Trevor Marshall I have warned about this problem in several peer reviewed papers. For example, Marshall and I state the following about correctly identifying microbe DNA in this Current Opinions in Rheumatology paper:
“What are we actually measuring? Genetic science has not yet noticed the elephant in the room – the microbial DNA and RNA that the human microbiome exudes from infected cells. This contaminates the samples of “human DNA” being analyzed.”
Well…Quake and team noticed the elephant in the room. And doing so made a dramatic difference in the results they obtained! I am extremely excited to see how their new findings impact microbiome research in the years to come.