Manipulate IDO metabolites in IBD – antIDOte

The gut microbiome is fundamental to health. Loss of the fragile equilibrium within this complex ecosystem is involved in numerous immune-related diseases including inflammatory bowel disease (IBD), for which there is a great unmet medical need both of new therapeutic approaches and biomarkers. Tryptophan (Trp) is an essential amino acid required for protein biosynthesis and it is also a biochemical precursor of metabolites that have major effects on mammalian physiology. The kynurenine pathway (KP) is one of the Trp metabolism pathways in the gastrointestinal tract and depends on indoleamine 2,3-dioxygenase (IDO) 1 which is expressed in both immune and epithelial cells. The KP is modulated by the gut microbiome and is over-activated in IBD. Here, we will (i) explore the role of specific Trp metabolites, downstream of IDO1, on gut inflammation ; (ii) develop a therapeutic strategy based on the modulation of the KP and (iii) evaluate the role of Trp metabolites as biomarkers in IBD.