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The gastrointestinal mucus system in health and disease

Abstract

Mucins—large, highly glycosylated proteins—are important for the luminal protection of the gastrointestinal tract. Enterocytes have their apical surface covered by transmembrane mucins and goblet cells produce the secreted gel-forming mucins that form mucus. The small intestine has a single unattached mucus layer, which in cystic fibrosis becomes attached, accounting for the intestinal manifestations of this disease. The stomach and colon have two layers of mucus; the inner layer is attached and the outer layer is less dense and unattached. In the colon, the outer mucus layer is the habitat for commensal bacteria. The inner mucus layer is impervious to bacteria and is renewed every hour by surface goblet cells. The crypt goblet cells have the ability to restitute the mucus layer by secretion, for example after an ischaemic challenge. Proteases of certain parasites and some bacteria can cleave mucins and dissolve the mucus as part of their pathogenicity. The inner mucus layer can, however, also become penetrable to bacteria by several other mechanisms, including aberrations in the immune system. When bacteria reach the epithelial surface, the immune system is activated and inflammation is triggered. This mechanism might occur in some types of ulcerative colitis.

Key Points

  • Gastrointestinal mucus is the first line of defence against bacteria

  • The mucus layer in the small intestine is freely movable and carries bacteria distally

  • In cystic fibrosis, the small intestinal mucus is not freely movable, which might explain the intestinal symptoms of this disease

  • The colon handles its large bacterial load with a two-layered mucus system, in which the inner layer normally remains impenetrable to bacteria.

  • Defective functioning of the inner mucus layer of the colon might be a pathophysiological mechanism for colitis and infectious diseases

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Figure 1: Simplified model of a gel-forming mucin produced by goblet cells and transmembrane mucins attached to the apical membrane of enterocytes.
Figure 2: The organization of epithelium and mucus in the gastrointestinal tract.
Figure 3: Mucus secretion from the colon surface epithelium and crypts during ischaemia and reperfusion.
Figure 4: Model of mechanisms that could affect the inner mucus layer properties and potentially cause ulcerative colitis.

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Acknowledgements

The authors' research is supported by the Swedish Research Council, The Swedish Cancer Foundation, The Knut and Alice Wallenberg Foundation, IngaBritt and Arne Lundberg Foundation, Sahlgren's University Hospital (LUA-ALF), Wilhelm and Martina Lundgren's Foundation, Torsten och Ragnar Söderbergs Stiftelser, The Sahlgrenska Academy, National Institute of Allergy and Infectious Diseases (U01AI095473, the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH), and The Swedish Foundation for Strategic Research—The Mucus–Bacteria–Colitis Center (MBC) of the Innate Immunity Program.

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Correspondence to Gunnar C. Hansson.

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Johansson, M., Sjövall, H. & Hansson, G. The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol 10, 352–361 (2013). https://doi.org/10.1038/nrgastro.2013.35

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