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Alterations of phospholipid concentration and species composition of the intestinal mucus barrier in ulcerative colitis: A clue to pathogenesis

Published on Nov 1, 2009in Inflammatory Bowel Diseases 4.00
· DOI :10.1002/ibd.20993
Annika Braun10
Estimated H-index: 10
(University Hospital Heidelberg),
Irina Treede3
Estimated H-index: 3
(University Hospital Heidelberg)
+ 11 AuthorsRobert Ehehalt13
Estimated H-index: 13
(University Hospital Heidelberg)
Cite
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 μg protein and 745 ± 148 pmol/100 μg protein) compared to that of patients with CD (3223 ± 1519 pmol/100 μg protein and 2450 ± 431 pmol/100 μg protein) and to controls (3870 ± 760 pmol/100 μg protein and 2790 ± 354 pmol/100 μg 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. Inflamm Bowel Dis 2009
  • References (60)
  • Citations (90)
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References60
Newest
Published on Mar 7, 2008in Journal of Biological Chemistry
Bill Davis8
Estimated H-index: 8
,
Grielof Koster17
Estimated H-index: 17
+ 8 AuthorsColin H. Macphee34
Estimated H-index: 34
Abstract There is increasing evidence that modified phospholipid products of low density lipoprotein (LDL) oxidation mediate inflammatory processes within vulnerable atherosclerotic lesions. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is present in vulnerable plaque regions where it acts on phospholipid oxidation products to generate the pro-inflammatory lysophsopholipids and oxidized non-esterified fatty acids. This association together with identification of circulating Lp-PLA2 levels as...
Published on Nov 6, 2007in Annals of Internal Medicine 19.32
Wolfgang Stremmel73
Estimated H-index: 73
(University Hospital Heidelberg),
Robert Ehehalt13
Estimated H-index: 13
(University Hospital Heidelberg)
+ 1 AuthorsMax Karner10
Estimated H-index: 10
(University Hospital Heidelberg)
Background: Although long-term steroid treatment is discouraged in ulcerative colitis, alternatives are lacking when therapy with immunosuppressant drugs fails. An insufficient level of phosphatidylcholine in colonic mucus is a possible pathogenetic factor for ulcerative colitis. Objective: To see whether steroid withdrawal is easier with retarded-release phosphatidylcholine or placebo in adults with chronic steroid-refractory ulcerative colitis. Design: Randomized, double-blind, placebo-control...
Published on Sep 14, 2007in Journal of Biological Chemistry
Irina Treede3
Estimated H-index: 3
,
Annika Braun10
Estimated H-index: 10
+ 9 AuthorsWolfgang Stremmel73
Estimated H-index: 73
Abstract We recently showed that mucus from patients with ulcerative colitis, a chronic inflammatory disorder of the colon, is characterized by a low level of phosphatidylcholine (PC) while clinical studies reveal that therapeutic addition of PC using slow release preparations is beneficial. The positive role of PC in this disease is still elusive. Here we tested the hypothesis that exogenous application of PC has anti-inflammatory properties using three model systems. First, human Caco-2 cells ...
Published on Sep 1, 2007in Journal of Immunology 4.72
Jan Wehkamp42
Estimated H-index: 42
(University of Tübingen),
Guoxing Wang7
Estimated H-index: 7
(University of Tübingen)
+ 10 AuthorsMatthias Schwab24
Estimated H-index: 24
(University of Tübingen)
Ileal Crohn′s disease (CD), a chronic mucosal inflammation, is characterized by two pertinent features: a specific decrease of Paneth cell-produced antimicrobial α-defensins and the presence of mucosal-adherent bacteria. A mutation in NOD2, the muramyl dipeptide recognition receptor, is found in some patients, which leads to an even more pronounced α-defensin decrease. However, the underlying mechanism remains unclear for the majority of patients. In this study, we report a reduced expression in...
Published on Aug 1, 2007in Inflammatory Bowel Diseases 4.00
Alexander Swidsinski15
Estimated H-index: 15
(HSU: Humboldt State University),
Beate C. Sydora13
Estimated H-index: 13
(U of A: University of Alberta)
+ 6 AuthorsLevinus A. Dieleman34
Estimated H-index: 34
(U of A: University of Alberta)
Background: Migration is an important virulence factor for intestinal bacteria. However, the role of bacterial mobility in the penetration of viscous mucus and their spatial organization within the colon is relatively unknown. Methods: Movements of fecal bacteria were assessed in gels of varying agarose concentrations and were compared with patterns of bacterial distribution observed in colons from conventional and Enterobacter cloacae-monoassociated mice. Bacteria were visualized using fluoresc...
Published on Jul 1, 2007in Current Opinion in Gastroenterology 2.74
Jan Wehkamp42
Estimated H-index: 42
,
Michael Schmid4
Estimated H-index: 4
,
Eduard F. Stange56
Estimated H-index: 56
Purpose of review Recently published studies presenting novel and relevant information on defensins and other antimicrobial peptides in Crohn's disease and ulcerative colitis are reviewed. Recent findings Different clinical localizations of Crohn's disease are associated with different deficiencies in epithelial and leukocyte antimicrobial peptide expression. As compared with ulcerative colitis, Crohn's disease of the colon is characterized by an impaired induction of beta defensins, and antimic...
Published on Mar 1, 2007in Gut 17.94
AlexanderSwidsinski20
Estimated H-index: 20
(Charité),
Vera Loening-Baucke12
Estimated H-index: 12
(Charité)
+ 5 AuthorsYvonne Dörffel15
Estimated H-index: 15
(Charité)
Aim: To study the role of mucus in the spatial separation of intestinal bacteria from mucosa. Patients and methods: Mucus barrier characteristics were evaluated using histological material obtained by biopsy from purged colon, colon prepared with enema and material from untreated appendices fixed with non-aqueous Carnoy solution. Bacteria were evaluated using fluorescence in situ hybridization, with bacterial 16S RNA probes and related to the periodic acid Schiff alcian blue stain. Biopsies from...
Published on Dec 1, 2006in Journal of Histochemistry and Cytochemistry 2.37
Rob J. Longman2
Estimated H-index: 2
(BRI: Bristol Royal Infirmary),
Richard Poulsom60
Estimated H-index: 60
+ 3 AuthorsM. G. Thomas12
Estimated H-index: 12
(BRI: Bristol Royal Infirmary)
Mucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa. MUC1 expressi...
Published on Nov 28, 2006in Journal of Molecular Medicine
Christoph Moehle19
Estimated H-index: 19
,
Nikolaus Ackermann1
Estimated H-index: 1
(Heidelberg University)
+ 7 AuthorsGerdSchmitz78
Estimated H-index: 78
Loss of intestinal mucosa integrity is an important factor in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to characterize expression changes and allelic variants of genes related to intestinal epithelial barrier function in this disease. Therefore, ileal and colonic mucosal biopsies from nonaffected regions of patients with ulcerative colitis (UC) and Crohn’s disease (CD), as well as non-IBD probands, were subjected to Affymetrix DNA-microarray analysis. Real-...
Published on Aug 1, 2006in Annals of the New York Academy of Sciences 4.29
Jan Wehkamp42
Estimated H-index: 42
(Robert Bosch Hospital),
Eduard F. Stange56
Estimated H-index: 56
(Robert Bosch Hospital)
: Crohn's disease (CD), a chronic inflammatory disease of the intestinal mucosa is usually located in the small intestine (ileum) and or in the colon. Ileal CD has been linked to a mutation in the NOD2 gene, a bacterial recognition protein. A disturbed antimicrobial defense as provided by an arsenal of different epithelial defensins seems to be a critical factor in disease pathogenesis. Defensins are antimicrobial peptides and in the ileum are mainly expressed in Paneth cells (PCs), epithelial c...
Cited By90
Newest
Published on Feb 17, 2019in Inflammatory Bowel Diseases 4.00
Urszula Daniluk2
Estimated H-index: 2
(UMB: Medical University of Białystok),
Jaroslaw Daniluk9
Estimated H-index: 9
(UMB: Medical University of Białystok)
+ 7 AuthorsMichal Ciborowski13
Estimated H-index: 13
(UMB: Medical University of Białystok)
Metabolic profiling might be used to identify disease biomarkers. The aim of our study was to determine the usefulness of untargeted metabolomics analysis to detect differences in serum metabolites between newly diagnosed and untreated pediatric patients with Crohn’s disease (CD) or ulcerative colitis (UC) in comparison with a control group (Ctr). Moreover, we investigated the potential of profiling metabolomics and inflammatory markers to improve the noninvasive diagnosis of CD and UC in childr...
Published on Jun 1, 2019in Journal of Cellular Biochemistry 3.45
Lei Shi1
Estimated H-index: 1
(Beijing University of Chinese Medicine),
Yi Dai1
Estimated H-index: 1
(Hyogo University of Health Sciences)
+ 7 AuthorsJunxiang Li3
Estimated H-index: 3
(Beijing University of Chinese Medicine)
Published on Apr 16, 2019in PLOS ONE 2.78
Katja Kalenyak1
Estimated H-index: 1
(Leipzig University),
Romy M. Heilmann12
Estimated H-index: 12
(Leipzig University)
+ 2 AuthorsIwan A. Burgener15
Estimated H-index: 15
Background Inflammatory bowel disease (IBD) and food-responsive diarrhea (FRD) are common chronic enteropathies in dogs, of which the exact pathogenesis has not been fully understood. In people dyslipidemia has been reported in patients with IBD, and potential therapeutic benefits of polyunsaturated fatty acids (PUFA) in the treatment of IBD have been investigated. Studies on the phospholipid profile in dogs with IBD and FRD are still lacking. Aim To investigate the systemic phospholipid profile...
Published on Apr 1, 2019in Journal of Pharmacy and Pharmacology 2.39
Angela Effinger1
Estimated H-index: 1
(University of Bath),
Caitriona M. O'Driscoll23
Estimated H-index: 23
(UCC: University College Cork)
+ 1 AuthorsNikoletta Fotaki11
Estimated H-index: 11
(University of Bath)
OBJECTIVES:Drug product performance in patients with gastrointestinal (GI) diseases can be altered compared to healthy subjects due to pathophysiological changes. In this review, relevant differences in patients with inflammatory bowel diseases, coeliac disease, irritable bowel syndrome and short bowel syndrome are discussed and possible in vitro and in silico tools to predict drug product performance in this patient population are assessed. KEY FINDINGS:Drug product performance was altered in p...
Published on Feb 27, 2019
Silvia Torrecillas1
Estimated H-index: 1
,
Daniel Montero36
Estimated H-index: 36
+ 2 AuthorsMarisol Izquierdo51
Estimated H-index: 51
Terrestrial protein and lipid sources are commonly used as substitutes for marine fishery-derived raw ingredients in fish diets. However, their use is related with several side-effects on marine fish performance, health, or disease resistance. Physical barriers of the skin, gills, and gut constitute the primary defense mechanism of fish. Skin mucus mucosal mucins, water, proteins, ions, and lipids determine the physical, chemical, and protective characteristics of skin mucus. Very little is know...
Published on Feb 1, 2019in Nature microbiology 14.30
Eric A. Franzosa23
Estimated H-index: 23
(Broad Institute),
Alexandra Sirota-Madi4
Estimated H-index: 4
(Broad Institute)
+ 24 AuthorsHimel Mallick8
Estimated H-index: 8
(Broad Institute)
The inflammatory bowel diseases (IBDs), which include Crohn’s disease (CD) and ulcerative colitis (UC), are multifactorial chronic conditions of the gastrointestinal tract. While IBD has been associated with dramatic changes in the gut microbiota, changes in the gut metabolome—the molecular interface between host and microbiota—are less well understood. To address this gap, we performed untargeted metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n = ...
Published on Jan 30, 2019in Clinical Microbiology Reviews 17.75
Hengameh Chloé Mirsepasi-Lauridsen6
Estimated H-index: 6
(SSI: Statens Serum Institut),
Bruce A. Vallance46
Estimated H-index: 46
(UBC: University of British Columbia)
+ 1 AuthorsAndreas Munk Petersen21
Estimated H-index: 21
SUMMARY Gut bacteria play a key role in initiating and maintaining the inflammatory process in the gut tissues of inflammatory bowel disease (IBD) patients, by supplying antigens or other stimulatory factors that trigger immune cell activation. Changes in the composition of the intestinal microbiota in IBD patients compared to that in healthy controls and a reduced diversity of intestinal microbial species are linked to the pathogenesis of IBD. Adherent invasive Escherichia coli (AIEC) has been ...
Published on Jan 1, 2019in Nature microbiology 14.30
Carina L. Chittim1
Estimated H-index: 1
(Harvard University),
Ana Martínez-del Campo3
Estimated H-index: 3
(Harvard University),
Emily P. Balskus22
Estimated H-index: 22
(Harvard University)
The essential nutrient choline is metabolized by gut bacteria to the disease-associated metabolite trimethylamine (TMA). However, most of the choline obtained via the diet and present in the human body is incorporated into larger metabolites, including the lipid phosphatidylcholine (PC). Here, we report that many choline-utilizing gut microorganisms can hydrolyse PC using a phospholipase D (PLD) enzyme and further convert the released choline to TMA. Genetic and in vitro characterization of the ...
Published on Dec 1, 2018in Scientific Reports 4.01
Brigida Rusconi2
Estimated H-index: 2
(WashU: Washington University in St. Louis),
Xuntian Jiang20
Estimated H-index: 20
(WashU: Washington University in St. Louis)
+ 3 AuthorsPhillip I. Tarr63
Estimated H-index: 63
(WashU: Washington University in St. Louis)
Necrotizing enterocolitis (NEC) remains a major challenge in neonatology. Little is known about NEC pathophysiology apart from the presence of pre-event gut dysbiosis. Here, we applied broad range metabolomics to stools obtained 1–5 days before NEC developed from 9 cases (9 samples) and 19 (32 samples) controls matched for gestational age at birth and birth weight. The 764 identified metabolites identified six pathways that differ between cases and controls. We pursued sphingolipid metabolism be...
Published on Sep 15, 2018in International Journal of Molecular Sciences 4.18
Bjoern Titz14
Estimated H-index: 14
,
Raffaella M. Gadaleta1
Estimated H-index: 1
+ 5 AuthorsJulia Hoeng27
Estimated H-index: 27
Inflammatory bowel disease (IBD) represents a group of progressive disorders characterized by recurrent chronic inflammation of the gut. Ulcerative colitis and Crohn′s disease are the major manifestations of IBD. While our understanding of IBD has progressed in recent years, its etiology is far from being fully understood, resulting in suboptimal treatment options. Complementing other biological endpoints, bioanalytical “omics” methods that quantify many biomolecules simultaneously have great po...