title: Alterations of phospholipid concentration and species composition of the intestinal mucus barrier in ulcerative colitis: a clue to pathogenesis.
abstract: 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 a 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 microg protein and 745 +/- 148 pmol/100 microg protein) compared to that of patients with CD (3223 +/- 1519 pmol/100 microg protein and 2450 +/- 431 pmol/100 microg protein) and to controls (3870 +/- 760 pmol/100 microg protein and 2790 +/- 354 pmol/100 microg protein); overall, P = 0.0002 for ileal specimens and P < 0.0001 for colonic specimens. Independent of disease activity, patients suffering from UC showed an increased saturation grade of PC fatty acid residues and a 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.
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Braun
authors.forename: Irina
authors.initials: I
authors.lastname: Treede
authors.forename: Daniel
authors.initials: D
authors.lastname: Gotthardt
authors.forename: Anke
authors.initials: A
authors.lastname: Tietje
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zahn
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ruhwald
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schoenfeld
authors.forename: Thilo
authors.initials: T
authors.lastname: Welsch
authors.forename: Peter
authors.initials: P
authors.lastname: Kienle
authors.forename: Gerhard
authors.initials: G
authors.lastname: Erben
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Lehmann
authors.forename: Joachim
authors.initials: J
authors.lastname: Fuellekrug
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.forename: Robert
authors.initials: R
authors.lastname: Ehehalt
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003113:Colonoscopy; D005260:Female; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008875:Middle Aged; D009093:Mucus / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013109:Sphingomyelins / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010743:Phospholipids; D013109:Sphingomyelins