The impact of dietary proteins for mucosal homeostasis and inflammation

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Based on our preliminary findings, we hypothesize that dietary proteins are essential for the maintenance of a normal intestinal immune compartment and barrier function. Here, we aim to reveal the effects of dietary protein on intestinal barrier function and T cell activation in the healthy and inflamed gut. This will be addressed in three steps. A) Intestinal homeostasis by specific immune recognition of food proteins. We will study whether susceptibility to intestinal inflammation is linked with recognition of food protein by the adaptive immune system. Immunocompetent, Rag1 KO and IL-10-Foxp3 reporter mice fed conventional (Conv) or protein-free (FAF) diet will be analysed for immunological responses, colitis development and intestinal barrier function. B) Dietary protein affects membrane integrity via an altered microbiome and gene expression. We will dissect the impact of both components on colitis development and intestinal membrane integrity. The experimental approach includes faecal transplantation and/or administration of protein in the presence or absence of microflora. These experiments will provide important information about the effects of a diet-altered microbiome and changes in intestinal gene expression for increased susceptibility to colitis. C) Nutritional therapies in Crohns disease (CD) patients. To translate the murine findings to human disease, we will study whether T cell hyperactivation observed in CD patients can be controlled by nutrional therapy. Intestinal T cells from patients and controls will be analyzed before and after nutritional therapy (elemental or parenteral diet). Further, T cell activation in the peripheral blood will be compared between patients. The data will provide insight how dietary protein regulates mucosal and peripheral T cell activation influencing the intestinal barrier function.