Alterations of Phospholipid Concentration and Species Composition of the Intestinal Mucus Barrier in Ulcerative Colitis: A Clue to Pathogenesis

Background: Phospholipids are essential for the normal function of the intestinal mucus barrier. The objective of this study was to systematically investigate phospholipids in the intestinal mucus of humans Suffering from inflammatory bowel diseases, where it barrier defect is strongly supposed to be pathogenetic. Methods: Optimal mucus recovery was first validated in healthy mice and the method was then transferred to the endoscopic acquisition of ileal and colonic mucus from 21 patients with ulcerative colitis (UC), 10 patients with Crohn's disease (CD), and 29 healthy controls. Nano-electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to determine phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) in lipid extracts of mucus specimens. Results: Human and rodent mucus contained very similar phospholipid species. In the ileal and colonic mucus from patients suffering from UC, the concentration of PC was highly significantly lower (607 +/- 147 pmol/100 mu g protein and 745 +/- 148 pmol/100 mu g protein) compared to that of patients with CD (3223 +/- 1519 pmol/100 mu g protein and 2450 +/- 431 pmol/100 mu g protein) and to controls (3870 +/- 760 pmol/100 mu g protein and 2790 +/- 354 pmol/100 mu g protein), overall, P = 0.0002 for ileal specimens and P < 0.0001 tor colonic specimens. Independent of disease activity, patients suffering from UC showed an increased Saturation grade of PC fatty acid residues and it higher LPC-to-PC ratio. Conclusions: The intestinal mucus barrier of patients with UC is significantly altered concerning its phospholipid concentration and species composition. These alterations may be very important for the pathogenesis of this disease and underline new therapeutic strategies.