When you hear microbiome, you often think of the gut first. But as the University Hospital Erlangen explains, the microbiome includes much more – namely the entirety of all microorganisms that colonize the surfaces of the human body. Whether skin, lungs or digestive organs, mouth, throat, nose or genital tract: Microorganisms such as bacteria, viruses and fungi can be found everywhere. If their composition is right, people benefit from it. But what is the ideal microbiome? And what influence do trillions of invisible creatures have on health and disease processes? This will be examined in the future by a new facility at the University Hospital Erlangen: the Microbiome Department headed by Prof. Dr. Stephen P Rosshart.
“Humans are like planet earth to countless microorganisms. They live in it and they need it as their host,” explains Stephan Rosshart. On the other hand, the microorganisms are also enormously useful for humans: they protect them from pathogens, support their immune system, digest what they cannot digest themselves, or produce important nutrients. “The microbiome is involved in almost all physiological processes and thus de facto in almost all diseases,” says Prof. Rosshart. “Its influence has already been proven for many diseases – for example for inflammatory or degenerative diseases of the central nervous system such as multiple sclerosis and Alzheimer’s. We know that the gut-brain axis exists and that microbial substances, such as so-called metabolites, are produced in the gut that reduce inflammation. Microorganisms also play a decisive role in cancer, allergies, autoimmune diseases and infectious diseases such as influenza or sepsis.” In short: wherever inflammation occurs and where the immune system is called into action, the microbiome also plays its part.
Microbiome research is still young. The interactions and the optimal balance between microorganisms and host are therefore only beginning to be understood. For example, no conclusive scientific evidence has yet been found for the popular hygiene hypothesis: Put simply, this assumes that the risk of allergies or autoimmune diseases increases the “cleaner” (sterile) a society is, and that it decreases, the more “dirty” children grow up. “But it’s definitely not that simple,” emphasizes Prof. Rosshart. “Rather, we have to assume a multifactorial process and take into account many different environmental influences – such as our industrially produced food, the materials in our living spaces, the composition of the air, the climate, the microorganisms with which we come into contact, and many more. And then there’s the question of how it all interacts with our own microbiome.”
Little from the field of microbiomics has so far been used therapeutically. An example is stool transplantation: Here, the stool of a healthy donor is transferred to the intestine of another person who has been severely infected with the Clostridium difficile bacterium and is unable to treat common medicines. In this case, the healthy bacterial composition of the donor should contribute to the healing of the damaged intestine. Therefore, the goal of the new Erlangen department is to understand the microbiome and its optimal composition and to derive potential therapies for humans from this.
collaborative approach
Stephan Rosshart, who moved from the University Hospital Freiburg to Erlangen in January 2023, wants to build his new research department on collaboration and work closely with the areas of microbiology, virology, immunology, rheumatology, tumor research, gastroenterology and molecular neurology, among others. “I would like to get involved in basic research at the Friedrich-Alexander-University Erlangen-Nuremberg, but in accordance with the translational approach ‘from bench to bedside’, I would also like to carry out clinical studies with patients at the University Hospital Erlangen – for example with people suffering from persistent, suffer from recurring bacterial or fungal infections,” he explains.
Prof. Rosshart works with so-called “wildlings” – laboratory mice to which the natural microorganisms of wild mice have been transferred. “In order to be able to transfer our research results to humans, we need a suitable model organism. For some of our complex questions, this can neither be the Petri dish nor a conventional laboratory mouse, because laboratory mice live under very clean conditions, have hardly any contact with microorganisms and, as a result, have a relatively immature immune system. We humans, on the other hand, live in an unsterile world, are in daily contact with microorganisms and therefore have a mature immune system,” explains the researcher. “So if we want to study how the microbiome influences the immune response, inflammation, cancer, allergies and other disease processes, we need a model with microbial experience and a mature immune system, such as humans and wild mice have. This is exactly what we achieve by transferring microorganisms from wild mice to laboratory mice.” According to initial studies by Prof. Rosshart, wildlings are actually closer to humans than conventional laboratory mice. Accordingly, they have a higher predictive power for human physiological processes for numerous questions.
Career of Stephan Rosshart
Stephan Rosshart studied biology and human medicine at the Albert-Ludwigs-University of Freiburg and received his doctorate in 2010 from the Institute for Immunology there. After completing his medical training at the Department of Internal Medicine II (gastroenterology, hepatology, endocrinology and infectiology) at the University Hospital in Freiburg, he spent six years researching at the National Institutes of Health (NIH) in Bethesda, USA. During this time he developed the “Theory of the Natural Microbiota” and the resulting translational models for researching human diseases – such as the wildlings. In 2019 he returned to the University Hospital Freiburg, where he took over the management of the gnotobiotic (sterile and microbially controlled) animal husbandry of the Clinic for Internal Medicine II and – as part of the Emmy Noether program of the German Research Foundation – the Translational Microbiome Research Laboratory. Since January 2023 he has headed the microbiomics department of the University Hospital Erlangen.
