Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 39, Pages 15064-15069Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0803124105
Keywords
commensal bacteria; proteomics; ulcerative colitis; large intestine; colon cancer
Categories
Funding
- Centre for Cellular Imaging at University of Gothenburg
- Swedish Research Council [7461, 8646, 20680]
- Swedish Research Council provided equipment
- Swedish Cancer Foundation
- Swedish Foundation for Strategic Research-Mucosal Immunobiology and Vaccine Center
- IngaBritt and Arne Lundberg Foundation
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We normally live in symbiosis with similar to 10(13) bacteria present in the colon. Among the several mechanisms maintaining the bacteria/host balance, there is limited understanding of the structure, function, and properties of intestinal mucus. We now demonstrate that the mouse colonic mucus consists of two layers extending 150 mu m above the epithelial cells. Proteomics revealed that both of these layers have similar protein composition, with the large gel-forming mucin Muc2 as the major structural component. The inner layer is densely packed, firmly attached to the epithelium, and devoid of bacteria. In contrast, the outer layer is movable, has an expanded volume due to proteolytic cleavages of the Muc2 mucin, and is colonized by bacteria. Muc2(-/-) mice have bacteria in direct contact with the epithelial cells and far down in the crypts, explaining the inflammation and cancer development observed in these animals. These findings show that the Muc2 mucin can build a mucus barrier that separates bacteria from the colon epithelia and suggest that defects in this mucus can cause colon inflammation.
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