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


RESULTS
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.


CONCLUSIONS
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.
Johansson
Malin E V
ME
Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
Gustafsson
Jenny K
JK
Sjöberg
Karolina E
KE
Petersson
Joel
J
Holm
Lena
L
Sjövall
Henrik
H
Hansson
Gunnar C
GC
D000328:Adult; D000368:Aged; D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D003106:Colon / Q000382:microbiology; D016264:Dextran Sulfate / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D013997:Time Factors
D016264:Dextran Sulfate
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