Irritable bowel syndrome (IBS) is a widespread disorder for which no cure exists. Tryptophan may be an interesting amino acid to alleviate IBS symptoms, although a large inter-individual variability exists. This is caused by the limited knowledge on the complex host-microbe interactions involved in IBS and in tryptophan metabolism from both human and microbial side. In this project we aim to unravel the key factors for successful tryptophan intervention by gaining knowledge on key microbial players, key (tryptophan) metabolites and cellular responses at the intestinal epithelial level. Practically, we will first collect faecal samples from healthy volunteers and IBS patients. In a next step, we will use bioreactor technologies, microbial cell sorting techniques and tryptophan enrichment to create different microbial communities leading to a diversity in tryptophan (and other) metabolites. A selection of these microbiomes will then be added to a set of cell cultures, in which enterocytes, enteroendocrine and mast cells are combined. Finally, the most promising combinations will be characterised by molecular techniques and state-of-the-art metabolomics. The obtained knowledge on metabolic networks between the host and the microbial community upon tryptophan supplementation can be used for the development of tryptophan containing foods and food supplements, personalised nutrition for IBS patients and possibly also for other diseases in which the gut-brain axis plays a role.