An intimate crosstalk between the epithelial cells, the microbiota and the immune cells controls the integrity of the intestinal barrier. Tryptophan metabolism recently turned out as determinant in regulating intestinal homeostasis. In intestinal epithelial cells, tryptophan can be oxidized to generate intermediate metabolites (e.g. kynurenine) with immunosuppressive properties and fuel cytoplasmic NAD+. Activation of this pathway (termed the kynurenine pathway), through IDO1 induction, alters the integrity of the epithelial barrier through modification of the microbiota composition. It additionally impacts on intestinal stem cell determination. The quinolinate phosphoribosyltransferase (QPRT) catalyzes the last step of the kynurenine pathway and takes place downstream the immunosuppressive intermediates. The enzyme is aberrantly expressed in numerous cancer types including colorectal carcinoma. By combining engineered mouse models, ex vivo organoïd culture and in vitro experiments, we are currently exploring the consequences of the loss or gain of QPRT function in intestinal homeostasis in both physiological and pathological conditions as well as in tumor development.
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