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Bacteria Penetrate the Inner Mucus Layer before Inflammation in the Dextran Sulfate Colitis Model
Open accessAbstract
BACKGROUND: Protection of the large intestine with its enormous amount of commensal bacteria is a challenge that became easier to understand when we recently could describe that colon has an inner attached mucus layer devoid of bacteria (Johansson et al. (2008) Proc. Natl. Acad. Sci. USA 105, 15064-15069). The bacteria are thus kept at a distance from the epithelial cells and lack of this layer, as in Muc2-null mice, allow bacteria to contact the epithelium. This causes colitis and later on colon cancer, similar to the human disease Ulcerative Colitis, a disease that still lacks a pathogenetic explanation. Dextran Sulfate (DSS) in the drinking water is the most widely used animal model for experimental colitis. In this model, the inflammation is observed after 3-5 days, but early events explaining why DSS causes this has not been described. PRINCIPAL FINDINGS: When mucus formed on top of colon explant cultures were exposed to 3% DSS, the thickness of the inner mucus layer decreased and became permeable to 2 microm fluorescent beads after 15 min. Both DSS and Dextran readily penetrated the mucus, but Dextran had no effect on thickness or permeability. When DSS was given in the drinking water to mice and the colon was stained for bacteria and the Muc2 mucin, bacteria were shown to penetrate the inner mucus layer and reach the epithelial cells already within 12 hours, long before any infiltration of inflammatory cells. CONCLUSION: DSS thus causes quick alterations in the inner colon mucus layer that makes it permeable to bacteria. The bacteria that reach the epithelial cells probably trigger an inflammatory reaction. These observations suggest that altered properties or lack of the inner colon mucus layer may be an initial event in the development of colitis.
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“Failure of this protective barrier to separate bacteria from the epithelium is observed in a number of murine colitis models 15, 17.”
From The composition of the gut microbiota shapes the colon mucus barrier (2015) · cites this paper as [17]
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Metadata
- Authors
- Johansson, M. E. V., Gustafsson, J. K., Sjöberg, K. E., Petersson, J., Holm, L., Sjövall, H., & Hansson, G. C.
- Affiliations
- University of Gothenburg (SE)
- Uppsala University (SE)
- Corresponding author
- Hansson, Gunnar C.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-08-18
- Volume
- 5
- Issue
- 8
- Pages
- e12238
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2923597
- OpenAlex
- W1977781139
- Cited by
- 368
- References
- 31
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 18 · 2023: 26 · 2022: 27 · 2021: 17 · 2020: 17 · 2019: 28 · 2018: 19 · 2017: 22 · 2016: 24 · 2015: 22 · 2014: 30 · 2013: 39 · 2012: 21
- FWCI
- 15.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Swedish Cancer Foundation
- Stiftelsen för Strategisk Forskning
- Knut och Alice Wallenbergs Stiftelse (KAW2007.0118)
- Vetenskapsrådet (21027, 342–2004-4434)
- Göteborgs Universitet
- National Institute of Allergy and Infectious Diseases (U01AI095473)
- Topics
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- mucus permeability, ulcerative colitis, MUC2, commensal bacteria, colonic epithelium, pathogenesis of inflammation
- MeSH terms
- Adult, Aged, Animals, Bacteria, Colitis, Colon, Disease Models, Animal, Female, Humans, Intestinal Mucosa, Male, Mice, Inbred C57BL, Permeability, Time Factors, Dextran Sulfate, Mice
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