Research is increasingly revealing links between the composition of our microbiome and diseases such as diabetes, obesity and even Parkinson’s and depression. But does that also mean that the cause and solution for many diseases reside in our intestinal flora? A guide to hope and hype.
As you read this, trillions of microscopic creatures are crawling on and in your body. They are in your mouth, on your skin and especially in your intestines. In recent years, interest in that microbiome has exploded. Unfortunately, this has also led to a lot of myths and misconceptions, the science magazine said New Scientist recently fixed.
It starts with the size of that microscopic colony. According to some estimates, you are in the minority in your own body and our body contains ten microorganisms for every human cell, together accounting for about two kilograms of microbes dry on the hook. In reality there are a lot fewer: just over one for each human cell, a total of about 500 grams. That’s still quite spectacular. “We are half human, half bacteria,” says microbiologist Jeroen Raes (KU Leuven and VIB).
In a sense, these micro-organisms form an extra organ in our body. “It is a collaborative company that is of great importance for our health and the proper functioning of our body,” says Raes. Our intestinal flora plays a crucial role in the digestion of our food, but also in our defense against pathogens. “The bacteria in our intestines form a first line of defense because they compete with potentially harmful invaders,” says Raes. “In addition, our immune system uses the intestinal flora to teach itself what it should and should not respond to.”
In recent years, scientists have found links between the composition of our microbiome and all kinds of conditions, such as obesity and diabetes, but also osteoarthritis, Parkinson’s disease and chronic fatigue. For example, recent research shows that people with chronic fatigue syndrome have fewer copies of the bacterium Faecalibacterium prausnitzii in their intestines, which is known to produce anti-inflammatory substances. People with chronic inflammation of the intestine, such as Crohn’s disease, also have less Faecalibacterium prausnitzii in the intestinal flora. In people with osteoarthritis, the bacterium Collinsella aerofaciens is more often found, which scientists suspect produces substances that play a crucial role in the disease process.
Anyone who follows the reporting on research into our microbiome might therefore think that it has a hand in an increasingly large group of diseases. But is that also true? “The evidence is generally strongest for gastrointestinal disorders,” says microbiologist Willem van Schaik (University of Birmingham). For example, an influence of the microbiome has been clearly demonstrated for Crohn’s disease and ulcerative colitis, both of which are associated with intestinal inflammation.
Cause or effect?
In many other cases, the first question is whether the connections found are real. These often involve studies involving a limited number of subjects, and it is not clear whether the results are generally valid. “Many connections appear questionable upon further investigation,” says American microbiologist Jonathan Eisen (University of California). “For example, so-called ‘cancer microbiomes’ turned out to be due to careless analyzes and the ‘obesity microbiome’ also did not survive.”
If studies repeatedly find a statistical connection between all kinds of conditions and what is in our intestines, the next question is whether it is a causal relationship. “That is very difficult to demonstrate,” says Raes. “Further investigation often reveals other factors that undermine a causal relationship.”
The microbiome varies enormously from person to person and is related to, among other things, diet, age, which medicines you use and where you live. All of those factors can cloud the relationship between the microbiome and disease. Raes mentions Parkinson’s disease as an example, for which a link with the microbiome has also been found. But Parkinson’s patients often suffer from constipation. And the so-called transit time, or how long food takes in the body from entry to exit, appears to have a major influence on the composition of the microbiome. “It is not clear whether intestinal flora patterns are the cause of the disease or a consequence of the constipation,” says Raes.
A combination of both is also possible. For example, patients with Crohn’s disease are genetically more susceptible to the development of inflammation in the intestine. As a result, their intestinal flora is disrupted and bacteria that worsen inflammation gain the upper hand. Raes: “This creates a vicious circle in which the changed intestinal flora is both cause and effect.”
The arm of the microbiome apparently reaches far. For example, American researchers found a different intestinal bacterial community in people with Alzheimer’s disease. And at the end of last year, Dutch researchers reported in the journal Nature Communications a link between depression and the composition of the intestinal flora. People with depression were found to have more bacteria from the genera Lachnoclostridium, Dialister and Streptococcus in their intestines.
Does how we feel depend on what is happening a few floors lower in our intestines? According to Raes, that idea is not completely out of the question. For an explanation, scientists look to the so-called brain-gut axis, a nerve connection between the brain and the intestines through which communication takes place in both directions. “It is also known that our intestinal flora produces substances such as serotonin and dopamine, which influence the brain,” says Raes.
But even in this case, the question of whether there is a causal relationship is far from being clarified. Jos Bosch (Amsterdam UMC), who participated in the study on depression, points out that if you provide rats with intestinal bacteria that are linked to depression, the animals more often develop the rat equivalent of depression. “That suggests causality,” says Bosch. “There are still indications of a possible causal relationship, although they are still scarce.”
With the step from mouse and rat to human, you always have to be careful. Mice that were implanted with the intestinal flora of obese subjects became fatter. “But subjects who received the microbiome of slim people did not become slimmer,” points out microbiologist Alan Walker (University of Aberdeen). “What works in mice doesn’t always work in people.”
Walker listed in the trade journal Nature Microbiology recently some myths and misconceptions about the microbiome. The fact that most diseases have a typical signature in the intestinal flora is one of them. “In most cases, there is still insufficient evidence for a role of the microbiome,” says Walker.
Once a causal link between microbiome and disease has been demonstrated, the question remains whether you can do something about it by adjusting the bacterial community in patients. This can be done via a so-called fecal microbiota transfer or ‘poop transplant’, with micro-organisms from a healthy donor. This treatment has been proven effective against an infection with the bacterium Clostridioides difficile, which causes incessant diarrhea. “In that case, such a fecal transplant is extremely successful,” says Van Schaik. “For other conditions, results so far have been predominantly negative.”
The exception is again intestinal problems such as Crohn’s disease. According to an overview study in the journal PLoS One symptoms disappear after a fecal transplant in more than a third of patients.
Now, poop transplants are not the most convenient and pleasant treatment anyway. If microbiome-targeted treatments come in the future, they will likely be in the form of beneficial bacterial cocktails. “So far, research into probiotics has mainly focused on bacteria that are easy to grow and use in yogurt,” says Van Schaik. “But those are not the most important ones for our health.”
The Ghent spin-off MRM Health is working on probiotics against Crohn’s disease and ulcerative colitis, among other things. “The first clinical studies showed positive effects, but larger studies are needed before this drug can be brought to market,” says Raes, who works as a scientific advisor for the company.
Scientists are not only investigating the potential of the microbiome as a treatment. They suspect that our bacteria could also help detect diseases at an early stage. For example, they look for signals based on changes in the intestinal flora that could indicate the development of diabetes or colon cancer. And sometimes the microbiome seems to be a predictor of the course of the disease. For example, earlier this year Raes and his colleagues showed that patients with multiple sclerosis with certain bacteria in the intestines deteriorated more quickly. “That knowledge could help determine how aggressively to start treatment,” says Raes.
The scientific interest in the microbiome has not escaped the notice of many mercantile minds. Nutrition gurus give all kinds of tips to optimize your microbiome and thus your health, and a real ‘microbe diet’ has even been developed. Some companies offer expensive microbiome analyzes as a basis for personalized nutritional advice.
What at first glance seems to be based on the latest scientific insights, on closer inspection often turns out to be reheated food: eat a varied diet, lots of fiber and not too much ultra-processed junk. “We simply know too little at the moment about how we should specifically adjust the microbiome, and certainly not at an individual level,” says Raes.
In fact, it is not at all clear what exactly a ‘healthy’ microbiome looks like. “A healthy microbiome is one that doesn’t make you sick,” says Walker. “But that can be different for everyone. Some people have a lot of bacteria in their intestines that we associate with disease, and yet they are healthy. Others don’t have it and still get sick. We cannot say what a universal, optimal composition of intestinal flora is.”
To challenge unjustified claims about the microbiome, Jonathan Eisen created the Overselling the Microbiome award, which he presented to scientists who inflate the results of animal research or make it appear that you can make your microbiome healthier by exercising. to make. Eisen says he does not denounce the overstatement of the microbiome because he thinks it is unimportant. “On the contrary,” says Eisen. “I believe the microbiome is incredibly important, and that it could be a powerful tool in medicine in the future.”
But the road to that end is still long in most cases. Some promising avenues will turn out to be dead ends. If treatments become available, they may not work for everyone or have only a modest effect. To avoid people losing confidence in science and patients suffering from difficult-to-treat diseases becoming disappointed, scientists like Eisen say it is important to temper expectations.
“I strongly believe in the potential of the microbiome,” says Raes. “But patients currently expect more from treatments than what medical science can deliver. Something like that takes a lot of time, but we are taking steps in the right direction every day.”