Therapeutic Potential to Modify the Mucus Barrier in Inflammatory Bowel Disease

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Abstract

Recently, numerous studies have shown that disruption of the mucus barrier plays an important role in the exacerbation of inflammatory bowel disease, particularly in ulcerative colitis. Alterations in the mucus barrier are well supported by published data and are widely accepted. The use of fluorescence in situ hybridization and Carnoy’s fixation has revealed the importance of the mucus barrier in maintaining a mutualistic relationship between host and bacteria. Studies have raised the possibility that modulation of the mucus barrier may provide therapies for the disease, using agents such as short-chain fatty acids, prebiotics and probiotics. This review describes changes in the mucus barrier of patients with inflammatory bowel disease and in animal models of the disease. We also review the involvement of the mucus barrier in the exacerbation of the disease and explore the therapeutic potential of modifying the mucus barrier with short-chain fatty acids, prebiotics, probiotics, fatty acid synthase, H ₂S, neutrophil elastase inhibitor and phophatidyl choline.

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The microbiome in inflammatory bowel disease: current status and the future ahead.

Aleksandar D. Kostic, Ramnik Xavier, Dirk Gevers (2014)

Studies of the roles of microbial communities in the development of inflammatory bowel disease (IBD) have reached an important milestone. A decade of genome-wide association studies and other genetic analyses have linked IBD with loci that implicate an aberrant immune response to the intestinal microbiota. More recently, profiling studies of the intestinal microbiome have associated the pathogenesis of IBD with characteristic shifts in the composition of the intestinal microbiota, reinforcing the view that IBD results from altered interactions between intestinal microbes and the mucosal immune system. Enhanced technologies can increase our understanding of the interactions between the host and its resident microbiota and their respective roles in IBD from both a large-scale pathway view and at the metabolic level. We review important microbiome studies of patients with IBD and describe what we have learned about the mechanisms of intestinal microbiota dysfunction. We describe the recent progress in microbiome research from exploratory 16S-based studies, reporting associations of specific organisms with a disease, to more recent studies that have taken a more nuanced view, addressing the function of the microbiota by metagenomic and metabolomic methods. Finally, we propose study designs and methodologies for future investigations of the microbiome in patients with inflammatory gut and autoimmune diseases in general. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

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The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions.

Malin Johansson, Jessica M Holmén Larsson, Gunnar Hansson (2011)

The normal intestinal microbiota inhabits the colon mucus without triggering an inflammatory response. The reason for this and how the intestinal mucus of the colon is organized have begun to be unraveled. The mucus is organized in two layers: an inner, stratified mucus layer that is firmly adherent to the epithelial cells and approximately 50 μm thick; and an outer, nonattached layer that is usually approximately 100 μm thick as measured in mouse. These mucus layers are organized around the highly glycosylated MUC2 mucin, forming a large, net-like polymer that is secreted by the goblet cells. The inner mucus layer is dense and does not allow bacteria to penetrate, thus keeping the epithelial cell surface free from bacteria. The inner mucus layer is converted into the outer layer, which is the habitat of the commensal flora. The outer mucus layer has an expanded volume due to proteolytic activities provided by the host but probably also caused by commensal bacterial proteases and glycosidases. The numerous O-glycans on the MUC2 mucin not only serve as nutrients for the bacteria but also as attachment sites and, as such, probably contribute to the selection of the species-specific colon flora. This observation that normal human individuals carry a uniform MUC2 mucin glycan array in colon may indicate such a specific selection.

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The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system.

Thaher Pelaseyed, Joakim Bergström, Jenny Gustafsson … (2014)

The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel-forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine, mucus limits the number of bacteria that can reach the epithelium and the Peyer's patches. In the large intestine, the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells secrete not only the MUC2 mucin but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate-keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103(+) type. In addition to the gel-forming mucins, the transmembrane mucins MUC3, MUC12, and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization, suggesting that enterocytes might control and report epithelial microbial challenge. There is communication not only from the epithelial cells to the immune system but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Author and article information

Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 14 January 2016

Publication date Collection: January 2016

Volume: 8

Issue: 1

Electronic Location Identifier: 44

Affiliations

Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing 210002, China; jingdianjing99@ 123456126.com (J.S.); dr_shenxiao@ 123456126.com (X.S.); dr_liyi@ 123456126.com (Y.L.); dr_guozhen@ 123456126.com (Z.G.); dr_zuolugen@ 123456126.com (L.Z.); dr_zhaojie@ 123456126.com (J.Z.); dr_gulili@ 123456126.com (L.G.); dr_gongjf@ 123456126.com (J.G.); dr_lijieshou@ 123456126.com (J.L.)

Author notes

[* ]Correspondence: dr_juwiming@ 123456126.com ; Tel./Fax: +86-25-80863736

[†]

These authors contributed equally to this work.

Article

Publisher ID: nutrients-08-00044

DOI: 10.3390/nu8010044

PMC ID: 4728657

PubMed ID: 26784223

SO-VID: 5852d5e7-30db-4785-937d-f3d90ea3270a

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This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

Therapeutic Potential to Modify the Mucus Barrier in Inflammatory Bowel Disease

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Abstract

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Karger: Gastroenterology

Most cited references 87

The microbiome in inflammatory bowel disease: current status and the future ahead.

The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions.

The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system.

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