Bacteria penetrate the inner mucus layer before inflammation in the dextran sulfate colitis model

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...

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Bibliographic Details
Published in:PloS one 2010-08, Vol.5 (8), p.e12238
Main Authors: Johansson, Malin E V, Gustafsson, Jenny K, Sjöberg, Karolina E, Petersson, Joel, Holm, Lena, Sjövall, Henrik, Hansson, Gunnar C
Format: Article
Language:English
Subjects:
Adult
Aged
Analysis
Animal
Animal models
Animals
Bacteria
Bacteria - metabolism
Beads
Biochemistry/Macromolecular Chemistry
Cell culture
chemically induced
Colitis
Colitis - chemically induced
Colitis - metabolism
Colitis - microbiology
Colitis - pathology
Colon
Colon - microbiology
Colon cancer
Commensals
Dextran
Dextran Sulfate
Dextran Sulfate - pharmacology
Dextrans
Disease Models
Disease Models, Animal
Drinking water
Epithelial cells
Epithelium
Explants
Female
Fluorescence
Gastroenterologi
Gastroenterology and Hepatology
Gastroenterology and Hepatology/Inflammatory Bowel Disease
Glycoproteins
Humans
Immunology/Innate Immunity
Inbred C57BL
Infiltration
Inflammation
Inflammatory bowel disease
Inflammatory bowel diseases
Intestinal Mucosa
Intestinal Mucosa - metabolism
Intestinal Mucosa - microbiology
Large intestine
Male
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
MEDICIN
MEDICINE
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
metabolism
Mice
Mice, Inbred C57BL
Microbiology
Microbiology/Innate Immunity
Mucin
Mucins
Mucus
pathology
Permeability
pharmacology
Rodents
Small intestine
Sulfates
Time Factors
Tumors
Ulcerative colitis
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Summary: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. 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0012238