Modulation of the intestinal barrier by the intestinal microbiota - Role of dietetic factors and the mucosal immune system

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The intestinal barrier is a complex functional entity consisting of mechanical components, but also immunological, neuronal and paracrine signals. On the one hand, it protects us against harmful components in the intestinal lumen, on the other, it allows absorption of fluids and nutrients required for survival. Moreover, it controls the intestinal microbiota, and in turn, the microbiota is one of the major regulators of the barrier function. Recently, data are cumulating that suggest a central role of the intestinal barrier for health and development of disease, the latter including both intestinal and extraintestinal diseases. Therefore, the interest in understanding this barrier in detail is now growing. In particular, we want to know how this barrier works, how we can assess barrier functions, and how we can support it. This is what is our project about.The major objective of our project is to study the complex interaction between diet, commensal bacteria and the host’s mucosa in the intestine in order to understand how the intestinal barrier is regulated under normal and inflammatory conditions. In particular, we aim to define molecular mechanisms how the intestinal microbiota and the intestinal mucosal immune system, either alone or together, affect the intestinal barrier and – vice versa – how the barrier may shape the intestinal microbiota and the intestinal mucosal immune system. In this context, the role of environmental factors such as dietary components known to modulate the barrier either directly or via alterations of the composition and function of the intestinal microbiota will be studied. In the first three years, all experiments will be performed in appropriate mouse models; afterwards the project will be extended to humans and human diseases.We expect new insights in dietetic, microbial and immunological factors modulating the intestinal barrier and therefore being of potential relevance for health and disease. From our approach, we also expect to define new strategies for future therapeutic interventions at the level of the intestinal barrier (e.g. dietary concepts, new probiotics, biologicals) with the potential to support barrier functions and thereby to prevent or treat diseases like IBD or intestinal infections. By doing this, we aim to increase our knowledge on how the intestinal barrier, the intestinal microbiota, and the intestinal immune system affect health and diseases.