The regulation of intestinal mucosal barrier glycosylation by the indigenous resident microflora has been proposed. Glycan legislation has been demonstrated in mice (1) and is a major event associated with the initial colonisation of the gut and ensures normal maturation of intestinal glycosylation profiles in addition to intestinal angiogenesis (2, 3). Little experimental evidence has been provides to demonstrate that the same processes are relevant in the human gut. Recent analysis of the glycosylation of the human mucus barrier has identified a library of glycan structures associated with distinct regions of the intestine (4), suggesting a regional glycosylation programme. We sought to address the glycan legislation hypothesis in man using the mucosal of patients undergoing intestinal diversion surgery. This operation diverts the faecal flow away from the distal colon and provides the opportunity to assess mucosal glycosylation with and without contact to the indigenous microflora. Intestinal mucosa from patients with ulcerative colitis (n=39), Crohn’s disease (n=24) and control (n=31) groups, with (n=34) and without (n=50) the diversion operation was collected from the same location in each case. The mucosa was tested for the expression of a series of known mucosal barrier glycosylated antigens. Glycan antigens were detected using a series of antibodies and plant lectins; Tn (antibody and Vicia Villosa lectin), sialyl, Tn, TF antigen (peanut lectin), sialyl Lewisa, sialyl-Lewisx, sulphoLewisa, O-acetylated sialic acids (antibodies PR3A5 and 6G4), poly-N-acetyl-Lactosamine (Maakia amurensis lectin I), alpha1-2 (Ulex europea lectin) and alpha1-6 linked (Aleuria Aurantia… agglutinin) fucose, alpha2-3 (Maakia Amurensis lectin II)and alpha2-6 (Sambucus Nigra lectin) linked sialic acids and Sda (Datura Bifloris lectin). Mucins MUC1, 2, 3A/B, 4, 5AC, 5B, 6, 7, 8, 11, 12 and 13 were detected with a series of gene specific antibodies. In addition metabolic labelling experiments with [3H]-glucosamine and sodium-[35S]-sulphate were used to monitor glycoprotein biosynthesis. Specific changes in mucosa from diverted patients were found detected for O-acetylated sialic acids with the 6G4 antibody and for the Sda antigen detected with the Datura bifloris lectin. No other glycan structure was altered. No change in MUC gene product expression was found. The response was related to the diversion operation and not to the normal or disease (UC or CD) profile. The data suggest that there is a selective and microflora related regulation of mucosal glycosylation corresponding to the glycan legislation hypothesis.