04/15/2026 | Research, English

A bond for life

Animals and plants collaborate with their microbes in surprising ways

Even though we do not notice them in our daily lives, they are always with us: countless bacteria and fungi that live in and on our body. Researchers worldwide have coined a term for the metaorganism that plants and animals form together with their microbiome: holobiont. It opens up a unique perspective on illness and health – and what it means to be a living being.

Eva Schissler

The average human body is made up of thirty billion cells. However, the number of microbes that colonize the body exceeds this figure many times over. The microbiome refers to the colony of microorganisms that live in our intestine, on our skin, basically everywhere in and on our body. And the topic is trending. A healthy gut flora is supposed to strengthen our immune system, boost our mood, and protect us from diseases like rheumatism, inflammation, or cancer. But the relationship between host and microbiome is complex and has implications far beyond well-being and healthcare.

Professor Filipe Cabreiro at the Institute of Genetics does not unequivocally share the enthusiasm for our microscopic cohabitants. He regards the relationship between complex organisms and their microbiomes as a Faustian bargain: microbes help us to repel pathogens, but they decrease our lifespan by several years in return. “Mice that live in a germ-free environment live longer than their conspecifics in nature,” says Cabreiro, who is also a Principal Investigator at the CECAD Cluster of Excellence on Aging Research and the Center for Molecular Medicine Cologne.

As a biochemist, Filipe Cabreiro uses model organisms such as the nematode Caenerohabditis elegans and mice to research how this ‘give and take’ interaction might affect humans, for example how the microbiome influences the effects of various medications. His colleague Bart Thomma came to the University of Cologne from the Netherlands in 2020 as an Alexander von Humboldt Professor. Together with Cabreiro, he organizes the course ‘Microbial Eecology’ as part of the ‘Quantitative Biology’ degree programme. Only he does not work with animal model organisms, but with plants. At the Institute for Plant Sciences and the CEPLAS Cluster of Excellence, he conducts research on the ways pathogens attack the microbiome of plants, weakening them and facilitating infestation.

“The roots actually function like an intestine, except that they are turned inside out,” the biologist explains. Plants also form a close team with the microbes that live directly on their roots or in the surrounding soil. And Thomma is not the only researcher interested in this relationship. Diverse CEPLAS working groups address the composition and function of the plant-associated microbiome and its role in plant health. The answers promise to help adapt crops to the new demands posed by climate change and a growing world population.

Plants calling for help

The term holobiont, composed of the Greek words hólos for ‘whole’ and bíos for ‘life’, originates from evolutionary biology. It was significantly influenced in the 1990s by the American biologist Lynn Margulis and describes a long history in which even the genomes of host organisms and their microbes have evolved together. Without the microbiome, complex life as we know it would not exist.

Filipe Cabreiro has been researching for decades how the microbiome of animal organisms influences the effects of medicines.

In plants, defining the boundaries of the holobiont is more difficult than in humans and other animals, as they are sessile organisms that are grounded in the soil via their roots: where is the beginning, where the end? Bart Thomma defines the plant holobiont as the plant and the associated microbiota that includes the so-called rhizosphere, the region around the roots that is influenced by what the plant gives off: “Although there are many microbes in the soil, their activity remains low. Close to the plant roots, there is a lot of activity. That is the region directly influenced by the plant.”

This allows the plant to do amazing things: not only can it excrete metabolites that keep harmful microbes at bay. If a pathogen does manage to overcome the microbiome’s defences, the plant can use specific molecules to recruit helpful microbes from the surrounding soil to help fight off the attacker. Experts call this phenomenon a “cry for help”. Thomma’s group studies this molecular warfare using the example of the wilt fungus Verticillium dahliae, which targets crops like tomatoes and cotton. The fungus secretes certain proteins to attack its host’s microbiome, thereby promoting infestation. The plant, in turn, mobilizes its own defences – and enlists the help of its allies, the microbes. “Attacking the host plant’s microbiome, and also undermining the plant’s cry for help, is one of the most important strategies of pathogens,” says Thomma.

Old medications, astonishing side effects

In animals, the microbiome mainly comprises microbes in the intestine and on the skin. One question that has hardly been posed so far is how the gut flora influences how drugs work. Filipe Cabreiro has been studying this effect for years. After obtaining his applied biochemistry degree in his home country of Portugal and completing his doctorate in Paris, Cabreiro went to University College London to work on his doctoral thesis. In 2008, he began his long-term research on metformin, a drug used to treat type II diabetes. It takes effect in the liver by ensuring that body tissue absorbs more glucose, thereby lowering blood sugar levels.

Metformin was first approved in 1957 – a time when clinical trials were not as rigorous as they are today. Some side effects and other potential uses surprise researchers to this day. It has also proven effective in treating cardiovascular conditions, and there are indications that it may inhibit neurodegeneration, thus slowing down the aging process. Due to its proven effectiveness over decades, it remains a first-line antidiabetic drugs and is on the World Health Organization’s list of essential medicines. And yet: “Today metformin would no longer be approved because of its numerous interactions,” Cabreiro points out.

Previous research has clearly demonstrated that metformin affects the gut flora: it changes its composition and increases Escherichia coli or E. coli – a group of bacteria with a bad reputation, as some of them cause infection. In addition to promoting the growth of E. coli, metformin also alters the function of the bacteria, causing them to produce metabolites that change host physiology. In particular, some of these metabolites, such as agmatine, can regulate lipid metabolism and host longevity in both worms and flies.

Bart Thomma observes a ‘war of molecules’: pests try to disable plants’ immune defences, whilst the plants call for help from the soil.

According to Cabreiro, the effect of drugs like metformin on and through the microbiome is still largely unknown, even in the case of cancer chemotherapies, which were often developed in the 1960s and 1970s. “Some substances are only activated by certain bacteria in the intestine. The individual composition of the microbiome could therefore explain, among other things, why these drugs are more effective in some people than in others,” says the researcher.

Even tumours have their own microbiomes, the composition of which might be crucial for selecting the right treatment: some microbes inhibit the active ingredient, while others enhance its effect. In colorectal cancer, for example, assessing the tumour’s specific microbial composition is particularly important when selecting a treatment.

Colleagues of Filipe Cabreiro’s in Heidelberg have recently even made a discovery about how antidepressants and antipsychotic drugs work. The antidepressant duloxetine, they found, causes confusion in the gut microbiome: certain bacteria absorb the drug because it resembles a molecule they can use in their metabolism. On the one hand, this reduces the amount of drug available for the host. On the other, the metabolites produced by these bacteria then reshape the overall structure of the microbiome. Cabreiro: “This is the reason why drugs such as the neuroleptic risperidone are associated with weight gain. It took us long to understand that what we are seeing is an interaction with the microbiome.”

Outnumbered by microbes

Bart Thomma believes that influencing the microbiome is crucial to breeding drought- and disease-resistant plants. Besides genetic modification, a cocktail of microbes that act against certain pathogens or compensate for nutrient deficiencies and stress in plants could be developed in the future. “We are gaining a better understanding of how the microbiome changes in response to stress or disease, and how metabolism and the microbiome influence each other,” says the biologist.

However, Thomma identifies another understudied topic in the long shared history of living creatures: interactions among microorganisms may be even more important than interactions between individual microbes and the host. Throughout evolutionary history, bacteria, fungi, algae, and protozoa have interacted with each other for much longer, forging beneficial alliances and developing joint survival strategies. From an evolutionary perspective, the microbes’ cooperation with plants and animals is but the blink of an eye. Thomma: “As organisms, we may be larger and more complex, but microbes outnumber us and are much older.”

When he thinks about the co-evolution of animal holobionts, Filipe Cabreiro clearly sees the advantages: “Without the enzymes produced by certain microorganisms, plants would be indigestible to us. Most animals – and we humans – would not even exist.” Seeing it that way, the few years they subtract from our lifespan seem like an acceptable price to pay.

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