Generated image of the microbiome
© Adobe Stock/Emiliia
The microbiome is a large microbial community in our body
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The one and a half kilogram community in our intestines

Strengthening our microbiome with a pill so that it can effectively fight diseases? HZI researchers are striving to make this vision of the future a reality.

Let's start with a wedding celebration. The bride has just given a speech and is now opening the buffet. There is only one problem: There are too many guests. This is because some unwanted guests have sneaked in. Fortunately, the invited guests have more practice in “active queuing”. This way, many of the unwanted guests at the buffet go away empty-handed. They leave the wedding hungry. For the celebration, this is a blessing. Who wants uninvited guests?

“The situation is similar in our intestines: The fuller and more diverse the microbiome there is, the more difficult it is for some rather harmful microorganisms to settle, because there is less food left for the unwanted intruders,” says scientist Dr. Lisa Osbelt-Block, who is researching the microbiome and microbiome-based therapies in Prof. Till Strowig's team at the Helmholtz Centre for Infection Research (HZI). But this is by no means the only mechanism by which the microbiome protects us.

Diversity is also good in the gut

The microbiome is like a huge community of subtenants in our intestines: around one and a half kilograms of microorganisms, mainly bacteria, but also viruses, fungi and yeasts. In recent years, research on the microbiome has exploded, and it is increasingly apparent that the influence of the microbiome on our health and our lives is huge. Not only do the bacteria break down food components, which is essential for our digestion, they also produce important vitamins and messenger substances. Changes in the microbiome have been observed in various types of intestinal diseases. Its contribution to the development of the diseases is currently being researched. The microbiome could also play a role in the development of various types of cancer. There is also evidence that it even influences aspects of our behavior, such as the development of depression. The cause and effect of all these impacts have not yet been conclusively clarified, but it is clear that the microbiome plays an important role.

This offers great potential for new therapeutic approaches. To do this, we would “just” need to know which of the approximately 1000 bacterial species that colonize our intestines are more beneficial and which are problematic. “It's very complex and varies from person to person: Some strains of the same species – such as Escherichia coli – can have beneficial or adverse effects, which makes everything even more complicated. We are only just beginning to understand these complex interactions. But we do know whether a few types of bacteria tend to be more positive or more negative,” says Osbelt-Block.

Portrait Dr Lisa Osbelt-Block
© HZI/Verena Meier
Lisa Osbelt-Block is researching the microbiome at the HZI

Who actually lives in our gut?

“Really beneficial bacteria are, for example, so-called lactobacilli, which are present in yogurt, for instance. Then there are bacteria that are part of the natural microbiome, but could be harmful under certain conditions and in larger numbers. These bacteria are called pathobionts. And finally, there are a large number of bacteria that are considered to be rather neutral. They are called commensals and, depending on their interactions with other bacteria or in response to certain environmental factors, can have rather bad or good properties.

“The commensals can act like the invited wedding guests: They occupy many niches and thus prevent unfavorable bacteria from settling,” says Osbelt-Block. However, occupying such niches is only a small part of the health-preserving effect that the microbiome has on us. Among other things, it can positively influence numerous metabolic processes in our body through messenger substances and strengthen the immune system. Conversely, however, an unfavorably composed microbiome can put a strain on the body and promote the development of diseases.

Antibiotics don't just kill bad germs

What has an unfavorable effect on the composition of the microbiome? First and foremost, a wide range of medications, especially antibiotics, says Osbelt-Block. This is because they attack many types of bacteria in a non-specific way – including the “good” ones. “I would like to emphasize that antibiotics are among the greatest achievements of modern medicine and it is right that we cannot imagine treatment without them today. But they also damage the microbiome, which is why they should not be used lightly,” she says.

The problem is exacerbated by increasing antibiotic resistance. For example, after antibiotics are administered, pathogens that are resistant to antibiotics have even more space to spread due to the death of other sensitive bacteria. To address this global problem of antibiotic resistance, researchers at the HZI's Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) are looking for bacteria in the soil that produce interesting substances as part of the citizen science project MICROBELIX, in which anyone can participate. Another working group at the HZI is researching, among other things, active substances produced by fungi.

Researchers like Lisa Osbelt-Block and Till Strowig are working towards a better understanding of the microbiome – and the ability to modify it in a targeted way. “If we can identify certain findings and imbalances and have effective levers to counteract them, for example by positively influencing the microbiome through a specific diet or the ingestion of certain substances, then this opens up a completely new approach to treatment,” says Till Strowig.

Till Strowig in a laboratory
© HZI/Verena Meier
Till Strowig heads the HZI department "Microbial Immune Regulation"

Your microbiome, your personal therapy

And this approach is ideally personalized, in line with the concept of personalized medicine. The researchers' vision is something like this: A patient suffering from a particular disease not only gives a blood sample at the doctor's office, but also a stool sample. The microbiome is analyzed in the stool sample – which has implications for diagnostics and therapy. “If certain imbalances are found in the microbiome, it may be possible to deduce from this that a particular drug will work better or worse or have stronger side effects, and adjust the therapy accordingly,” says Strowig.

Taking this idea a step further, a problem can be treated not only at the disease level, but also at the microbiome level: “If, for example, we have found an imbalance that adversely affects the course of a disease, then in the future we may be able to combat this imbalance specifically with a capsule of certain bacterial strains,” says Osbelt-Block.

Although such an approach still seems a long way off, it is not unrealistic. In the United States, for example, the first two microbiome-based therapies have recently been approved, in which mixtures of different bacterial species are introduced into the intestines of patients in a targeted manner. This means that serious and recurrent infections with the hospital germ Clostridioides difficile can now be treated effectively. A first customized treatment for the intestinal microbiome. Lisa Osbelt-Block is hopeful that many more will follow in the future.

And what can you do today to strengthen your microbiome? Although she emphasizes that this varies from person to person, Lisa Osbelt-Block can at least give a few general recommendations: less stress, more exercise, a high-fiber diet. “And don't overdo it with excessive disinfection in your immediate surroundings. Too much hygiene can impair the diversity of the microbiome,” says Osbelt-Block.

Text: Christian Heinrich

This text was published in the HZI magazine InFact in the issue Autumn 2024.

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