Microbe-host cross-talk is an important determinant of human health with maintenance of gut
epithelial barrier function being a crucial process in this intricate relationship. Compromising the gut barrier has been associated with an increased risk for development of chronic inflammation, allergy, diabetes or metabolic disease. While the gut barrier controls (micro-)nutrient absorption, it also fends off antigens or xenobiotics. One of the contaminants of highest health concern is arsenic (As), which affects more than 200 million people worldwide, causing cancer, cardiovascular and metabolic diseases.
Due to a higher internal exposure to ingested As, patients with a compromised gut barrier function may become more susceptible to its detrimental health effects. Moreover, besides its carcinogenicity, As may also disrupt energy homeostasis and induce inflammatory response, thereby aggravating disease development and/or progression.
In this project, I will use a dynamic simulator of the human gut, integrated with cell models of the intestinal barrier, to obtain a mechanistic understanding of how As affects the host-microbe interplay. The in vitro findings, validated in a gnotobiotic mice model will let me draw conclusions whether As exposure constitutes an additional risk factor for diseases where gut barrier function plays an key role. This is relevant in the context of diseases such as diabetes and chronic inflammation, both of which are on the rise in Western society.