Intestinal barrier dysfunction in inflammatory bowel diseases.

Published on Jan 1, 2009in Inflammatory Bowel Diseases4.005
· DOI :10.1002/ibd.20539
Michael A. McGuckin50
Estimated H-index: 50
(UQ: University of Queensland),
Rajaraman Eri23
Estimated H-index: 23
(UQ: University of Queensland)
+ 2 AuthorsGraham L. Radford-Smith42
Estimated H-index: 42
(QIMR: QIMR Berghofer Medical Research Institute)
The etiology of human inflammatory bowel diseases (IBDs) is believed to involve inappropriate host responses to the complex commensal microbial flora in the gut, although an altered commensal flora is not completely excluded. A multifunctional cellular and secreted barrier separates the microbial flora from host tissues. Altered function of this barrier remains a major largely unexplored pathway to IBD. Although there is evidence of barrier dysfunction in IBD, it remains unclear whether this is a primary contributor to disease or a consequence of mucosal inflammation. Recent evidence from animal models demonstrating that genetic defects restricted to the epithelium can initiate intestinal inflammation in the presence of normal underlying immunity has refocused attention on epithelial dysfunction in IBD. We review the components of the secreted and cellular barrier, their regulation, including interactions with underlying innate and adaptive immunity, evidence from animal models of the barrier's role in preventing intestinal inflammation, and evidence of barrier dysfunction in both Crohn's disease and ulcerative colitis. (Inflamm Bowel Dis 2008)
  • References (178)
  • Citations (337)
📖 Papers frequently viewed together
2,638 Citations
1,419 Citations
799 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Åsa V. Keita (Linköping University)H-Index: 17
#2Sa´ad Salim (Linköping University)H-Index: 1
Last. Johan D. Söderholm (Linköping University)H-Index: 45
view all 8 authors...
Crohn's disease, a chronic inflammation of the bowel, is a multi-factorial condition where uncontrolled immune responses to luminal bacteria occur in genetically predisposed individuals. The first observable clinical signs are small ulcers that form at a specialised form of epithelium, follicle-associated epithelium (FAB). The FAB covers immune inductive sites, Peyer's patches, which function primarily as sensory areas that sample the externaI gut environment. Dendritic cells are one of the key ...
64 CitationsSource
#1Rana Al-Sadi (UNM: University of New Mexico)H-Index: 17
#2Dongmei Ye (UNM: University of New Mexico)H-Index: 16
Last. Thomas Y. Ma (UNM: University of New Mexico)H-Index: 32
view all 4 authors...
The IL-1β-induced increase in intestinal epithelial tight junction (TJ) permeability has been postulated to be an important mechanism contributing to intestinal inflammation of Crohn’s disease and other inflammatory conditions of the gut. The intracellular and molecular mechanisms that mediate the IL-1β-induced increase in intestinal TJ permeability remain unclear. The purpose of this study was to elucidate the mechanisms that mediate the IL-1β-induced increase in intestinal TJ permeability. Spe...
222 CitationsSource
#1Junichi NishimuraH-Index: 22
#2Hiroyuki SaigaH-Index: 12
Last. Kiyoshi TakedaH-Index: 117
view all 13 authors...
Secretory leukocyte protease inhibitor (SLPI) has multiple functions, including inhibition of protease activity, microbial growth, and inflammatory responses. In this study, we demonstrate that mouse SLPI is critically involved in innate host defense against pulmonary mycobacterial infection. During the early phase of respiratory infection with Mycobacterium bovis bacillus Calmette-Guerin, SLPI was produced by bronchial and alveolar epithelial cells, as well as alveolar macrophages, and secreted...
33 CitationsSource
#1Chad K. Heazlewood (UQ: University of Queensland)H-Index: 1
#2Matthew C. CookH-Index: 36
Last. Michael A. McGuckin (UQ: University of Queensland)H-Index: 50
view all 17 authors...
Background MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterised the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis.
433 CitationsSource
#1Akira Kanoh (UTokyo: University of Tokyo)H-Index: 6
#2Hideyuki Takeuchi (UTokyo: University of Tokyo)H-Index: 26
Last. Tatsuro Irimura (UTokyo: University of Tokyo)H-Index: 48
view all 6 authors...
Abstract Mucus hypersecretion occurs as a consequence of the Th2 immune response in epithelia, yet it was not previously known whether the degree of O-glycosylation was modulated under such conditions. A colonic carcinoma cell line LS174T was used to assess the effect of interleukin (IL)-4 on the mRNA levels of eight pp-GalNAc-Ts. A three- to four-fold increase in pp-GalNAc-T1, T4, and T7 levels was observed. Lysates of untreated or IL-4-treated cells were examined for their ability to transfer ...
17 CitationsSource
#1Lisa A. SimmsH-Index: 6
#2James D. DoeckeH-Index: 23
Last. Graham L. Radford-SmithH-Index: 42
view all 6 authors...
Background and aims: Reduced ileal Paneth cell alpha-defensin expression has been reported to be associated with Crohn9s disease (CD), especially in patients carrying NOD2 mutations. The aim of this study was to independently assess whether NOD2, alpha-defensins and CD are linked. Methods: Using quantitative RT-PCR, we measured the mRNA expression levels of key Paneth cell antimicrobial peptides (DEFA5, DEFA6, LYZ, PLA2G2A), inflammatory cytokines (IL6, IL8), and a marker of epithelial cell cont...
186 CitationsSource
#1Rachel J. Adams (UQ: University of Queensland)H-Index: 3
#2Sharise P. Heazlewood (UQ: University of Queensland)H-Index: 1
Last. Timothy H. Florin (UQ: University of Queensland)H-Index: 42
view all 6 authors...
IgG Antibodies Against Common Gut Bacteria Are More Diagnostic for Crohn's Disease Than IgG Against Mannan or Flagellin
46 CitationsSource
#1Sean L. Barnes (UVA: University of Virginia)H-Index: 3
#2Alda Vidrich (UVA: University of Virginia)H-Index: 10
Last. Steven M. Cohn (UVA: University of Virginia)H-Index: 25
view all 8 authors...
SAMP1/Fc mice develop spontaneous ileitis that shares many features with human Crohn’s disease. One of the earliest features of ileitis in SAMP1/Fc mice is an increase in the number of ileal goblet and intermediate cells. Resistin-like molecule β (RELMβ) is a goblet cell-specific, cysteine-rich peptide previously shown to function as part of the innate immune response. In this study, we examined the role of expression of RELMβ in the initiation of ileal inflammation in SAMP1/Fc mice. RELMβ was h...
26 CitationsSource
#1Salma Akram (Mayo Clinic)H-Index: 4
#2Joseph A. Murray (Mayo Clinic)H-Index: 13
Last. Susan C. Abraham (Mayo Clinic)H-Index: 48
view all 7 authors...
Background & Aims: Autoimmune enteropathy is a rare cause of intractable diarrhea associated with circulating gut autoantibodies and a predisposition to autoimmunity. It is rarely observed in adults, with only 11 cases reported to date. Methods: Fifteen adults with autoimmune enteropathy were identified at the Mayo Clinic, Rochester, from May 2001–June 2006. The demographic, clinical, and treatment data were abstracted from their records. Results: The study population was 87% white, 47% female, ...
128 CitationsSource
#1Michael A. McGuckin (UQ: University of Queensland)H-Index: 50
#2Alison L. Every (University of Melbourne)H-Index: 13
Last. Philip Sutton (University of Melbourne)H-Index: 28
view all 11 authors...
Background & Aims: The MUC1 mucin is expressed on the cell surface of epithelial cells lining the gastric mucosa. Epidemiologic studies suggest that functional allelic variations in the MUC1 gene may play a role in human susceptibility to Helicobacter pylori-associated pathologies, including gastric adenocarcinoma. We have evaluated the impact of Muc1 expression on the colonization and pathogenesis of gastric Helicobacter infections. Methods: Wild-type and Muc1-deficient mice were infected with ...
132 CitationsSource
Cited By337
#1Benjamin E. Mead (MIT: Massachusetts Institute of Technology)H-Index: 5
Last. Jose Ordovas-MontanesH-Index: 8
view all 12 authors...
Barrier tissue epithelia play an essential role in maintaining organismal homeostasis, and changes in their cellular composition have been observed in multiple human diseases. Within the small intestinal epithelium, adult stem cells integrate diverse signals to regulate regeneration and differentiation, thereby establishing overall cellularity. Accordingly, directing stem cell differentiation could provide a tractable approach to alter the abundance or quality of specialized cells of the small i...
#1Michael O Wellington (U of S: University of Saskatchewan)H-Index: 1
#2Kimberley Hamonic (U of S: University of Saskatchewan)
Last. Daniel A. Columbus (U of S: University of Saskatchewan)H-Index: 8
view all 6 authors...
Background: The independent and interactive effects of dietary fiber (DF) and threonine (Thr) were investigated in growing pigs challenged with either systemic E. coli lipopolysaccharide (LPS) or enteric Salmonella Typhimurium (ST) to characterise their effect on intestinal barrier function. Results: In experiment 1, intestinal barrier function was assessed via oral lactulose and mannitol (L:M) gavage and fecal mucin analysis in pigs challenged with E. coli LPS and fed low fiber (LF) or high fib...
#1Xuelei Cao (Cleveland Clinic)
#2Lei Sun (Cleveland Clinic)
Last. Andrei I. Ivanov (Cleveland Clinic)H-Index: 14
view all 6 authors...
BACKGROUND: Disruption of the gut barrier is an essential mechanism of inflammatory bowel diseases (IBDs) contributing to the development of mucosal inflammation. A hallmark of barrier disruption is the disassembly of epithelial adherens junctions (AJs) driven by decreased expression of a major AJ protein, E-cadherin. A group of isoxazole compounds, such as E-cadherin-upregulator (ECU) and ML327, were previously shown to stimulate E-cadherin expression in poorly differentiated human cancer cells...
#1Zhichu Chen (University of Murcia)
#2Diana Ceballos-Francisco (University of Murcia)H-Index: 4
Last. M. Ángeles Esteban (University of Murcia)H-Index: 32
view all 4 authors...
Abstract The effects of skin wounds on the intestinal barrier function and the beneficial effects of the dietary administration of Shewanella putrefaciens (known as SpPdp11) in gilthead seabream (Sparus aurata L.) were studied. Two replicates of fish were fed a commercial diet (control, CON) or CON diet enriched with 109 cfu g−1 SpPdp11 (SP diet) for 30 days. After this time, half of the fish were sampled, while the others were injured below the lateral line (wounded fish, W) and fed the same di...
#1Yonghong Shi (NAU: Nanjing Agricultural University)H-Index: 2
#2Waseem Ali Vistro (NAU: Nanjing Agricultural University)H-Index: 2
Last. Qiusheng Chen (NAU: Nanjing Agricultural University)H-Index: 9
view all 10 authors...
Abstract It is conceivable that pathological conditions can cause intestinal barrier disruption and innate immune dysfunction. However, very limited information has been reported on the effect of seasonal variance on intestinal barriers and innate immunity. The present study was designed to investigate the seasonal variance in intestinal epithelial barriers and the associated innate immune response of turtle intestines during hibernation and nonhibernation periods. Goblet cells (GCs) demonstrate...
#1Yu Tao (CPU: China Pharmaceutical University)
#2Mengfan Yue (CPU: China Pharmaceutical University)H-Index: 4
Last. Yue Dai (CPU: China Pharmaceutical University)H-Index: 22
view all 9 authors...
Intestinal epithelial barrier dysfunction is deeply involved in the pathogenesis of inflammatory bowel diseases (IBD). Arctigenin, the main active constituent in Fructus Arctii (a traditional Chinese medicine), has previously been found to attenuate colitis induced by dextran sulfate sodium (DSS) in mice. The present study investigated whether and how arctigenin protects against the disruption of the intestinal epithelial barrier in IBD. Arctigenin maintained the intestinal epithelial barrier fu...
#1Tom Breugelmans (University of Antwerp)H-Index: 14
#2Hanne Van Spaendonk (University of Antwerp)H-Index: 2
Last. Benedicte Y. De Winter (University of Antwerp)H-Index: 26
view all 11 authors...
BACKGROUND AND AIMS: There is evidence for a disturbed intestinal barrier function in inflammatory bowel diseases (IBD) but the underlying mechanisms are unclear. Because mucins represent the major components of the mucus barrier and disturbed mucin expression is reported in the colon of IBD patients, we studied the association between mucin expression, inflammation and intestinal permeability in experimental colitis. METHODS: 4 kDa FITC-dextran intestinal permeability and the expression of cyto...
#1Na Dong (NEAU: Northeast Agricultural University)H-Index: 10
#2Chenyu Xue (NEAU: Northeast Agricultural University)H-Index: 1
Last. Anshan Shan (NEAU: Northeast Agricultural University)H-Index: 2
view all 7 authors...
Salmonella typhimurium (S.T) is a common cause of acute, self-limiting food-borne diarrhea with severe intestinal inflammation and intestinal barrier damage. Oleanolic acid (OA), isolated from almost 2,000 plant species, has been shown to have anti-inflammatory roles. The purpose of this study was to investigate the potential protective effects of oleanolic acid (OA) on S.T-induced diarrhea and enteritis and to elucidate its anti-inflammatory mechanisms. A total of eighty BALB/c mice (4-weeks-ol...
3 CitationsSource
#1Zhao Deng (HAU: Huazhong Agricultural University)H-Index: 3
#2Chenbin Cui (HAU: Huazhong Agricultural University)
Last. Jian Peng (HAU: Huazhong Agricultural University)H-Index: 17
view all 7 authors...
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. We previously found that fish skin gelatin hydrolysate fraction 3 (FSGHF3) isolated from fish skin gelatin hydrolysate, could exert antioxidant effects and maintain tight junction in IPEC-J2 cells. Further HPLC-ESI-QqQ-MS results revealed that this fraction mainly included some peptides. Here, we aim to evaluate...
#1Jia-Zhen Wu (Guangzhou University of Chinese Medicine)H-Index: 5
#2Yuxuan Gan (Guangzhou University of Chinese Medicine)
Last. Qi-Duan Wu (Guangzhou University of Chinese Medicine)H-Index: 1
view all 13 authors...
Abstract Intestinal mucositis causes great suffering to cancer patients who undergo chemotherapy and radiotherapy. Owing to the uncertain side effects of anticancer drugs to attenuate patients’ intestinal mucositis, many studies focused on traditional Chinese medicine (TCM). Patchouli alcohol (PA) is an active compound extracted from Pogostemon cablin, and has potent gastrointestinal protective effect. However, whether PA has an effect on intestinal mucositis is still unknown. Therefore, we esta...