Until recently, when bacteria were detected in your blood, you were in trouble. Blood was long considered sterile, meaning it was free of viable microorganisms such as bacteria. When pathogenic bacteria spread through the bloodstream, they can cause life-threatening septic shock.
But the use of DNA sequencing technology has made it easier for researchers to detect what had been reported as early as the late 1960s: bacteria can be found in the blood without causing disease.
As we begin to map and understand the complex microbial ecosystem that lives in our gut and elsewhere in the body, we are asking an important question: Is there a blood microbiome?
Detecting a fingerprint in blood
Our large intestine is not sterile; it is teeming with bacteria. But it was long believed that some parts of the body were devoid of microorganisms. The brain. Bones. Various internal fluids, such as synovial fluid and peritoneal fluid. And, most importantly, blood.
Blood is made up of a liquid called plasma, filled with red blood cells whose main function is to carry oxygen to our cells. It also carries white blood cells, whose important role is to monitor and fight infections, as well as platelets, which participate in clotting.
Although we can sequence the complete DNA of any bacteria in the bloodstream, the most commonly used technique is 16S rRNA gene sequencing. I’ve always admired physicists’ penchant for quirky names: gluons, neutrinos, and charm quarks. By comparison, molecular biologists tend to be more restrained. Yes, we have genes like Sonic hedgehog and proteins called scramblases; in general, however, we have to deal with the coldness of “16S rRNA.” RNA is a molecule with many uses. Messenger RNA (or mRNA) acts as a disposable copy of a gene, a template for producing a specific protein. Transfer RNA (or tRNA) delivers the building blocks of a protein to where they are assembled. Ribosomal RNA (or rRNA), on the other hand, is the main component of our cells’ huge protein factories, the ribosomes. One of its subunits is made up of, among other things, a particular strand of RNA known as 16S rRNA.
The interesting thing about the gene that codes for this 16S rRNA molecule is that it is very old and mutates slowly. By reading its precise sequence, scientists can determine which species it belongs to. Most studies of the so-called blood microbiome use this technique to find out which species of bacteria are present in the blood being analyzed. However, this test is limited by the fact that dead bacteria also have DNA. Just because the DNA of the 16S rRNA gene of a specific bacterial species was detected in a person’s blood does not mean that those bacteria were alive. For there to be a microbiome in the blood, those microorganisms must be alive.
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Which brings us to another important point of discussion. For scientists to acknowledge the existence of a blood microbiome, they must first agree on a definition of the microbiome, which remains a point of contention. In 2020, when companies were all too happy to advertise their services to test your gut microbiome and interpret, they claimed, what it meant for your health, experts in the field came together to agree on what the word “microbiome” meant. “We’re missing, did they writea clear and commonly accepted definition of the term “microbiome.” For example, do viruses count? A microbiome implies life, but the virus is an exceptional case: it has the genetic blueprint for life, but cannot reproduce on its own.
These experts proposed that the word “microbiome” refers to the sum of two things: the microbiota, that is, the living microorganisms, and their theater of activity. That is, the Earth is not just the life forms it supports, but also all of their individual components, the traces they leave behind, and the environmental conditions in which they thrive or die. The microbiome is made up of bacteria and other microorganisms, yes, but also of their proteins, lipids, sugars, DNA and RNA molecules, and the signaling molecules and toxins that are exchanged in their theater of activity. (This is where viruses have been classified, by the way: not as part of the living microbiota, but as part of the theater of activity of the microbiome.)
The microbiome is a community, and that community has a distinct habitat.
So what does the evidence say? Is our blood really home to a thriving community of microorganisms, or is something else going on?
Transient and sporadic
The first studies on the so-called blood microbiome were small wingspan. The amounts of bacteria observed by DNA sequencing were tiny. If this microbiome existed, it seemed to be scarce, more ” asteroid field in real life » than «asteroid field in movies».
So what were the few bacteria in the blood that weren’t known to be contaminants doing if they weren’t part of a healthy microbiome? The authors lean toward another explanation that’s been proposed for many years: These bacteria are transient. They end up in the blood from other parts of the body, either because of a minor leak or because they’re actively transported into the blood by agents such as dendritic cells. Like pedestrians wandering onto the highway, these bacteria don’t normally live in the blood, but you can see them there if you look at the right time.
Putting the medical cart before the horse
The story of the blood microbiome could end there and be just another interesting example of scientific research focusing on a curious finding, testing a hypothesis, and eventually disproving it (or at least providing strong evidence against it). But given the motivations of modern research and the social media focus on scholarly literature, two slightly disturbing aspects are worth discussing.
Scientists are increasingly being pushed to find practical applications for their research. It is not enough, for example, to study bacteria that survive incredibly high temperatures; we need to be assured that theDNA replication enzyme The genetic makeup of these bacteria will one day be used in labs around the world to conduct research, identify criminals and test samples for the presence of a pandemic-causing coronavirus.
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But if the blood microbiome is imaginary, we are just chasing ghosts. This is reminiscent of the days when scientists published microRNA signatures in the blood for every possible cancer. When I reviewed the literature on the subject as part of my undergraduate studies, I realized that the multiple signatures reported for a single cancer were were barely riding. These were just chance findings. Compare enough variables in a small sample and you will find what appears to be an association.
You have been warned.
Key message:
- Our blood has long been considered sterile, meaning free of viable microbes, unless a dangerous infection gets into it, causing sepsis.
- Studies have shown the presence of bacteria in the blood of some healthy humans, leading to the hypothesis that, just like our gut, our blood is host to a microbiome.
- The largest study ever conducted on the subject has provided strong evidence against this hypothesis. It appears that when non-pathogenic bacteria end up in our blood, it is temporary and occasional.
