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The intestinal tract forms an important barrier against xenobiotics while allowing nutrients to pass. In ulcerative colitis (UC), a chronic inflammatory bowel disease, this barrier function is impaired leading to an abnormal immune response and inflammation of the colonic mucosa. Transporter proteins and metabolic enzymes are an integral part of the protective barrier in the gut and play an important role in the disposition of nutrients, toxins and oral drugs. In this study, the protein expression of 13 transporters and 13 enzymes was determined in the sigmoid and rectum of UC patients in endoscopic remission and during active inflammation. In inflamed con-ditions (endoscopic Mayo sub-score 1, 2 or 3), a significant decrease (q < 0.05) was observed in the median expression of the transporters P-gp (0.046 vs 0.529 fmol/mu g protein), MRP4 (0.003 vs 0.023 fmol/mu g protein) and MCT1 (0.287 vs 1.090 fmol/mu g protein), and the enzymes CYP3A5 (0.031 vs 0.046 fmol/mu g protein) and UGT2B7 (0.083 vs 0.176 fmol/mu g protein). Moreover, during severe inflammation, the decrease was even more pro-nounced. Expression levels of other proteins were not altered during inflammation (e.g., OATP2B1, CYP3A4, CYP2B6 and UGT2B15). The results suggest a decreased transport and metabolism of xenobiotics in the colon of UC patients during active inflammation potentially altering local drug concentrations and thus treatment outcome.