Do we have bacteria that live in our blood?
Most people have heard of intestinal flora. But now researchers are wondering: Can bacterial communities also exist in blood?
Our knowledge of bacteria in and on the body has taken a quantum leap in the last 20 years. Today, countless studies show that the microbes in the body – our microbiome – are closely linked to our health.
But for a long time we assumed that the barriers in the body, such as the skin and mucous membranes, kept bacteria out of the blood system, muscles and organs. Researchers believed that the inside of the body was sterile – bacteria-free – unless we contract a life-threatening infection where bacteria have entered the blood.
But in recent years, science has developed equipment that is sensitive enough to find microorganisms among the body's own cells. And now the picture is changing.
Studies in both animals and humans have shown that bacteria can be in tissues and organs like the liver, adipose tissue and brain tissue. Often these findings are linked to disease. For example, researchers have found bacteria and fungi in the brains of people with Alzheimer's disease.
Bacteria have also been detected in cancerous tumours.
The big question is clearly: How in the world did the bacteria get there? Could they have come via the blood? And if so, what were they doing there?
Bacteria in the blood of healthy people
The idea that bacteria can circulate in the blood of humans actually existed as early as the late 1960s. By then, a group of researchers had found traces of living bacteria in the blood of apparently healthy people.
A decade later, another group of researchers thought they had managed to show that bacteria grew in blood samples from healthy people.
And since the DNA sequencing methods developed around the turn of the millennium, a number of studies have found bacterial DNA in the blood of healthy people. Studies in animals have shown similar results.
The same bacterial groups often seem to recur, which could indicate that these microorganisms may be present in the blood of many people, according to a research review published in Frontiers of Cellular and Infection Microbiology in 2019.
The authors concluded that increasing evidence shows there is a human blood-microbiome in healthy people.
Does this mean that a community of living bacteria actually resides in our blood?
Sceptical of blood flora
Johannes Espolin Roksund Hov at the University of Oslo and his colleagues have just started a project to map bacteria in the blood.
Hov says that he is embarking on the research with a healthy dose of scepticism.
“The idea that there could be a circulating microbiome in the blood – a kind of blood flora – seems unlikely at the outset. But if it proves to be the case, this would be a fundamentally new biology,” he says.
“At the same time, so many researchers have found bacteria in the blood, so we have to be open to that possibility.”
Hov’s hesitancy is based on several reasons. For instance, the fact that studies are showing findings of bacteria in the blood does not necessarily mean that the microorganisms actually came from there.
Measurements might be incorrect
According to Hov there are also a lot of problems with the methods used.
“The amounts of bacteria we’re looking for are miniscule,” he says.
While bacteria abound in the gut and on the skin, the situation is probably completely different in the blood.
“It’s not like we observe all kinds of unknown spots when we look at blood through a microscope,” says Hov.
If you want to be able to find any bacteria among all the other cells in the blood, you need extremely sensitive measurement methods. This increases the likelihood that the bacterial DNA found does not actually originate in the blood, but in pollution from the environment.
Researchers have to follow a very strict system. All equipment used needs to be examined for bacteria. Even sterile water has occasionally been shown to contain tiny amounts of bacteria.
“It’s impossible to guarantee that not a single microorganism from the environment sneaks into the sample, and so we have to use statistical methods to ‘deduct’ pollution,” says Hov.
In addition, it is not easy to know if DNA findings in the blood originate from living bacteria, or if they are fragments of damaged microorganisms.
Hiding in the cells
Hov believes that another reason for scepticism is that a stable blood flora circulating in the blood does not quite fit with the experiences we have from before.
Bacteria typically grow on a surface, whereas the blood is a fluid in constant motion.
One possibility, however, is that the bacteria do not float around on their own but hide inside the body's own cells. We know that several types of bacteria and viruses can do this.
In that case, it might be that these bacteria are dormant in healthy people, but that certain influences can cause them to wake up and cause illness.
On the other hand, it may also be that bacteria that live in the blood can have a useful function, for example by training and calibrating our immune system.
All this is only speculation so far. We need much better scientific documentation before we can say that a natural blood flora like this exists, Hov believes.
What he thinks more likely, however, is that bacteria may be able to remain in the blood for shorter or longer periods.
The question then becomes: Where do these visiting bacteria come from?
Skin and mucous membranes are barriers to bacteria
Speculation has been rife about the origin of bacteria in the blood. Could we have been born with them?
Hov confirms that the researchers are considering whether the environment inside the uterus is not as sterile as we previously thought. He himself, however, believes in a more obvious source:
Our own bacterial flora.
A community of microorganisms grows on our skin and mucous membranes, and our guts contain formidable bacterial flora that feed on parts of the food we are not able to digest ourselves.
But our skin and mucous membranes are designed so that they form a barrier against both microorganisms and environmental substances.
The mucous membranes in the intestine, for example, have relatively good control over which substances are to be released through the intestinal wall. Substances like water and nutrients are allowed to enter the body, while microorganisms and many of the substances they create are kept out.
Previously, researchers considered this barrier to be impermeable.
“Our protection against the outside world is probably not completely perfect, so maybe bacteria can get into the blood even when you’re healthy,” says Hov.
“And if you have infections or the immune system is weakened, for example, the intestinal barrier might become more permeable.”
“Some studies have shown that the bacteria found in the blood are similar to those found in the intestine,” says Hov.
Bacteria might also be finding a way into the blood through holes or leaks in other barriers. One study found that bacteria in the blood were more similar to the flora found on the skin and in the mouth than to intestinal flora, according to the review from 2019.
If a lot of bacteria are found in the blood due to this kind of leakage through various barriers, it’s easy to imagine that they could have a negative impact on our health. But there's a lot about this we don’t understand yet.
An important question is whether the bacteria that researchers find in the blood are part of the mechanisms behind various diseases, or whether they are just a sign that the body is ill.
Hov and colleagues from Norway and the Baltics will investigate this question.
Liver disease and intestinal trouble
“We work with patients who have primary sclerosing cholangitis (PSC), a serious chronic liver disease for which there’s no good treatment,” says Hov.
Most patients with this disease also have ulcerative colitis, an inflammatory bowel disease. The researchers suspect that what happens in the intestine is related to the problems in the liver.
For example, can bacteria leak through the inflamed intestinal wall, circulate with the blood and then affect the liver?
Hov and his colleagues will map what they find in the blood of both healthy individuals and patients with PSC. Do the PSC patients have more bacteria in their blood? And if so, is there a pattern of bacteria that is characteristic of people with PSC?
If such a pattern actually exists, it would be important to investigate what the bacteria do.
On the one hand, they could be contributing to causing the disease. In that case, researchers may need to find out how bacteria affect the liver and how we can prevent them from causing harm.
On the other hand, it is also possible that bacteria in the blood are just the result of a severe intestinal inflammation. The bacteria are not necessarily a cause of the liver disease. But they may be a marker, providing a measure of how active the disease is.
More questions than answers
Possible links between disease and bacteria in the blood do not only apply to liver disease.
These microorganisms could also be important for type 2 diabetes, heart disease, Alzheimer's and Parkinson's disease, write the researchers behind an article published in Trends in Endocrinology & Metabolism in 2020.
So far, this field of research is characterized by far more questions than answers. Several tests need to be done to reveal if any diseases are caused by bacteria in the blood.
To find out if a bacterial flora exists in the blood, researchers will need to do large population-based studies to see if many people have a similar bacterial profile, Hov believes.
In addition, researchers should use different methods to look for bacteria. If they manage to get the same results with different procedures, the answer will be more convincing.
“There’s currently no consensus that a community of living bacteria exists in the blood,” says Hov.
“But there is considerable interest around phenomena where microbes in the blood are relevant to health and disease,” he says.