The effect of dietary AGEs on human gut epithelial models of health and disease.

We bake our foods to ensure its safety, but also to improve its taste, odor and appearance. The latter is closely related to the Maillard Reaction. When food is heated, this non-enzymatic reaction results in the modification of proteins by simple sugars (e.g. glucose) which is related to the development of flavor, color and aroma. These glycated proteins being formed, are also known as dietary Advanced Glycation End Products (AGEs). They are especially present in high temperature processed, low-moisture foods such as baked potatoes or bakery. It is estimated that we consume 25-75 mg of dAGEs daily, however it is not known if and how they can have an impact on intestinal health. It is hypothesized that their effect may be detrimental, since endogenously formed AGEs are linked to the development of for example cataract, cardiovascular diseases and neurodegenerative diseases. However, in these cases, body proteins get glycated wherefore they lose their functionality or get inflammatory properties and it is not known whether exposure to such proteins via the diet exerts similar effects. Hence, this project aims to unravel the effects of dAGEs on human epithelial models of health and disease, and to identify the receptors and pathways involved. Therefore, 3D in vitro models will established from healthy and cancerous human colon biopsies. The impact of dAGE exposure on these organoid models will be assessed with targeted as well as untargeted analysis methods. Throughout the project, the complexity of the model will be increased by including compartments mimicking the immune system and gut microbiota.