Our hypothesis, contrary to the prevailing models, is that the disease ulcerative colitis is due to defects in the inner mucosal layer of the colon that allow bacteria to penetrate it and trigger an inflammatory reaction when the bacteria reach the epithelial cells. We will now go on to examine the molecules and the changes they undergo in the large intestine so that the mucus first forms a dense mucus layer, sticks, then loosens and expands in volume and becomes a home for all the bacteria in the gut. Most of these events take place around the MUC2 mucin, which will be altered by cutting it in different places. Besides MUC2, there are many other proteins that we think or know are important for the proper functioning of the inner mucus layer. There are probably many different reasons why this inner mucus layer can fail, ranging from genetic defects in the MUC2 mucin to particularly aggressive bacteria that form, just as we have shown for a parasite, enzymes that can cause the inner mucus layer to break down. We will now collect material from a large number of patients with ulcerative colitis. In this material we will look for mutations in MUC2 and other interesting proteins, measure mucus thickness and especially mucus permeability. We will look at the composition of the mucus both by analyzing which genes are expressed and which proteins are present (proteomics) and study which bacteria are present and which proteins they produce.