Role of the intestinal barrier in inflammatory bowel disease

Department of Pathology and Laboratory Medicine, Emory University, 615 Michael Street, Atlanta, GA 30322, USA.
World Journal of Gastroenterology (Impact Factor: 2.37). 02/2008; 14(3):401-7.
Source: PubMed


A critical function of the intestinal mucosa is to form a barrier that separates luminal contents from the interstitium. The single layer of intestinal epithelial cells (IECs) serves as a dynamic interface between the host and its environment. Cell polarity and structural properties of the epithelium is complex and is important in the development of epithelial barrier function. Epithelial cells associate with each other via a series of intercellular junctions. The apical most intercellular junctional complex referred to as the Apical Junction Complex (AJC) is important in not only cell-cell recognition, but also in the regulation of paracellular movement of fluid and solutes. Defects in the intestinal epithelial barrier function have been observed in a number of intestinal disorders such as inflammatory bowel disease (IBD). It is now becoming evident that an aberrant epithelial barrier function plays a central role in the pathophysiology of IBD. Thus, a better understanding of the intestinal epithelial barrier structure and function in healthy and disease states such as IBD will foster new ideas for the development of therapies for such chronic disorders.

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Available from: Porfirio Nava, Sep 16, 2015
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    • "**Significant (p \ 0.01). Mann–Whitney testAuthor's personal copy alterations are hallmarks of a number of GI disorders, such as UC, CD, UC-associated colorectal cancer and CRC (Schmitz et al. 1999;Clayburgh et al. 2004;Usami et al. 2006;Laukoetter et al. 2008;Weber et al. 2008;Mees et al. 2009;Su et al. 2009). Luminal antigen uptake occurs via TJ discontinuities and epithelial gross lesions, which are likely to induce many other changes to the epithelium besides simply altering the TJ barriers (Hollander et al. 1986;Su et al. 2009;Lu et al. 2013). "
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    ABSTRACT: The synthesis of the proteins of the apical tight junctions (TJs) depends on a continuous supply of short-chain fatty acids (SCFAs) in colonic epithelium. No studies have evaluated the tissue contents of the TJs proteins in colon segments devoid of a fecal stream. To evaluate the contents of claudin-3 and occludin in the glands of colonic mucosa devoid of a fecal stream. Forty-five rats underwent a diversion of the fecal stream via a left side colostomy and distal mucous fistula. Three groups of 15 animals each were sacrificed at 6, 12 or 18 weeks after surgery. The presence and severity of colitis were defined by histology and inflammation grading scales, respectively. The expression of claudin-3 and occludin were evaluated by immunohistochemistry, and their contents were evaluated by computer-assisted image analysis. Mann-Whitney and Kruskal-Wallis tests were used to evaluate the results at a significance level of 5 % (p < 0.05). The colonic epithelium without a fecal stream had a higher degree of inflammation. Colonic glands without a fecal stream showed a reduction in claudin-3 content independent of the time and reduction in occludin content after 12 weeks of intestinal exclusion. The content of claudin-3 and occludin were mainly reduced at the apical surfaces of the colon glands, whereas segments retaining the fecal stream were maintained. The content of claudin-3 was not reduced with time, although the levels of occludin were reduced after 6 weeks and did not vary thereafter. Deficiencies in SCFAs decreased the content of claudin-3 and occludin in colonic glands with the areas of worst inflammation, confirming the importance of an adequate supply of SCFAs in maintaining the integrity of TJ proteins.
    Full-text · Article · Feb 2015 · Journal of Molecular Histology
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    • "Altered permeability has been reported in those suffering from CD [24, 26, 27]. Several studies have ascertained that CD patients have an abnormal increase in intestinal permeability to paracellular markers, such as polyethylene glycol 400, cellobiose, Cr-ethylenediaminetetraacetic acid (Cr-EDTA), and lactulose [24, 26, 27]. Further studies have also shown that healthy first-degree relatives of CD patients have increased intestinal permeability with evidence of antigenic stimulation [89]. "
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    ABSTRACT: The inflammatory bowel diseases (IBD) include Crohn's disease (CD) and ulcerative colitis. The disease may present at any age although the peak of presentation is the second and third decades of life. The incidences of these diseases are increasing around the world with the age of presentation getting younger. At present CD is incurable with colectomy being the treatment for severe UC. Although several pharmacological approaches are used to modulate the inflammatory response in IBD, few lead to histological healing and most have side effects. An alternative approach is to use enteral formulae given exclusively (EEN) to treat IBD. EEN requires the consumption of an elemental or polymeric formula, with the exclusion of all other nutrients, for a period of up to 12 weeks. The introduction of EEN as a therapeutic option for IBD was through prudent observation; however, EEN has become an established and reliable option for the treatment of paediatric IBD. Despite this, the mechanisms through which EEN induces disease remission are unknown and remain hypothetical. This review will discuss recent research into EEN both describing clinical features of EEN therapy and discussing the most up-to-date understanding of the mechanisms through which EEN may be reducing intestinal inflammation and inducing disease remission.
    Full-text · Article · May 2014
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    • "Colonic epithelial cells, which act as sentinels of the mucosal immune system, are critical to the barrier and absorptive functions of the colon [9, 10]. Human colonic epithelial cells express numerous inflammatory molecules, including cytokines, chemokines, and receptors, which allow them to communicate with the immune system [11]. NF-κB is critical for the maintenance of epithelial barrier function and modulation of immune responses. "
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