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How the microbial ecosystem inside our gut influences health and disease

Do bacteria in our gut cause cancer or even neurodegenerative diseases of the brain? Do they determine whether we are over-weight or skinny? And if so, how could we as humans take control over the billions of microorganisms that live inside us? The Eco-Systems Biology research group at the LCSB aims to answer these and other questions around the microbiome, the community of all microbial organisms that live in and on our body. In total, more than 1500 different species account for around 1.5 kg of our body mass. For the past five years, this eco-system of our body is the subject of intense study for its potentially tremendous impact on human health.

“We know that the balance between different types of microbes is important,“ says Prof Paul Wilmes, who leads the Eco-Systems Biology group at the LCSB. “However, it is not yet understood how disturbances of the balance, for instance through higher abundance of one type of microbes, can lead to different diseases such as cancer, metabolic disorders or even Parkinson’s disease.” Therefore, Wilmes and his team set out to study the interaction between different microbial compositions and the epithelial cells of the gut. They hypothesize that changes that could trigger disease will first be visible at this interface between the microbes and their human host.

Analysing stool samples from human volunteers, the researchers are first analysing which types of bacteria exist in diseased and healthy subjects. In a next step, they want to study the effect such differences have on the gut cells and whether this could be the cause of the disease. As experiments in human subjects would be too invasive to answer these questions and the gut-microbiome of mice is quite different from that of humans, Wilmes and his team developed a new in vitro model, called HuMiX. It is a so-called microfluidic device in which one can co-culture human epithelial cells of the human gut together with microbial communities. “We can expose human cells to different bacteria compositions and see what molecular pathways they might trigger in the gut under which conditions, ” explains Wilmes. The results can help in screening microorganisms for potential beneficial effects, such as anti-inflammatory properties, that could thus influence diseases, such as allergies or autoimmune disorders.

Recently, the team has taken HuMiX to the next level: MicroGUT is an in vitro model of the entire human gastrointestinal tract. Different units for each part of the gut are simulated to study what effects bacteria, nutrients and drugs elicit on human physiology. “We can use it to simulate certain processes in the individual segments of the gastrointestinal tract, like drug catabolism in the body, for instance,” Wilmes explains. The researchers now intend to use MicroGUT to assess pharmacokinetics on an individual basis without the need for animal models and, from there, to optimally personalise drug therapy.