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 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.
Braun
Annika
A
Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany.
Treede
Irina
I
Gotthardt
Daniel
D
Tietje
Anke
A
Zahn
Alexandra
A
Ruhwald
Rebecca
R
Schoenfeld
Ulrike
U
Welsch
Thilo
T
Kienle
Peter
P
Erben
Gerhard
G
Lehmann
Wolf-Dieter
WD
Fuellekrug
Joachim
J
Stremmel
Wolfgang
W
Ehehalt
Robert
R
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
D000305:Adrenal Cortex Hormones; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010743:Phospholipids; D013109:Sphingomyelins