Activation of bitter taste receptors tune innate immune responses in the gut epithelium during health and disease

The gastrointestinal tract represents the largest key interface between the human body and the external environment. It is a chemosensory organ in which the epithelium is equipped with elements from the taste signaling pathway that continuously monitor and discriminate between nutrients that need to be assimilated and harmful substances that need to be expelled. We hypothesize that bitter taste receptors on several human epithelial cell types can recognize bitter compounds as a harmful substance and elicit adequate immune responses to protect the gut. In addition, we aim to elucidate whether this chemosensory signaling process is altered in patients with obesity or inflammatory bowel disease (IBD) in which innate immune responses are affected. We will use state of the art techniques to measure the effect of bitter compounds on the production of antimicrobial peptides from Paneth cells and enterocytes, IL17E from tuft cells and mucin-2 from goblet cells in an epithelial cell line and in isolated primary crypts from organ donors and patients with obesity or IBD. The originality of this work lays in the demonstration whether and how bitter taste receptors in the human intestine are involved in the regulation of immune functions during health and disease. Specific diets or the enormous choice of available bitter taste receptor agonists that target these chemosensory signaling pathways may be considered as new therapeutic targets to tune innate immune responses in the human gut.