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Updated: May 14, 2026
Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with
Malin E V Johansson1, Jenny K Gustafsson, Jessica Holmén-Larsson
1Department of Medical Biochemistry, University of Gothenburg, , Gothenburg, Sweden.
Objective:
The inner mucus layer in mouse colon normally separates bacteria from the epithelium. Do humans have a similar inner mucus layer and are defects in this mucus layer a common denominator for spontaneous colitis in mice models and ulcerative colitis (UC)?
Methods And Results:
The colon mucus layer from mice deficient in Muc2 mucin, Core 1 O-glycans, Tlr5, interleukin 10 (IL-10) and Slc9a3 (Nhe3) together with that from dextran sodium sulfate-treated mice was immunostained for Muc2, and bacterial localisation in the mucus was analysed. All murine colitis models revealed bacteria in contact with the epithelium. Additional analysis of the less inflamed IL-10(-/-) mice revealed a thicker mucus layer than wild-type, but the properties were different, as the inner mucus layer could be penetrated both by bacteria in vivo and by fluorescent beads the size of bacteria ex vivo. Clear separation between bacteria or fluorescent beads and the epithelium mediated by the inner mucus layer was also evident in normal human sigmoid colon biopsy samples. In contrast, mucus on colon biopsy specimens from patients with UC with acute inflammation was highly penetrable. Most patients with UC in remission had an impenetrable mucus layer similar to that of controls.
Conclusions:
Normal human sigmoid colon has an inner mucus layer that is impenetrable to bacteria. The colon mucus in animal models that spontaneously develop colitis and in patients with active UC allows bacteria to penetrate and reach the epithelium. Thus colon mucus properties can be modulated, and this suggests a novel model of UC pathophysiology.
Insights
Human colons possess an inner mucus layer impenetrable to bacteria, unlike mouse models of colitis and active ulcerative colitis (UC) patients where bacteria reach the epithelium. This suggests mucus barrier defects are key in UC pathophysiology.
Area of Science:
- Gastroenterology
- Immunology
- Microbiology
Background:
- The colon's inner mucus layer typically prevents bacterial contact with the epithelium.
- Defects in this mucus barrier may contribute to colitis in mice and humans.
Purpose of the Study:
- To investigate the presence and function of a human inner colon mucus layer.
- To determine if mucus layer defects are common in spontaneous mouse colitis models and human ulcerative colitis (UC).
Main Methods:
- Immunostaining for Muc2 mucin in mouse and human colon samples.
- Analysis of bacterial localization within the mucus layer.
- Ex vivo penetration assays using fluorescent beads.
Main Results:
- All tested murine colitis models showed bacteria reaching the epithelium.
- Human sigmoid colon samples exhibited an impenetrable inner mucus layer.
- Colon mucus from active UC patients was highly penetrable by bacteria and beads, unlike remission patients and controls.
Conclusions:
- Normal human colons have an inner mucus layer that effectively blocks bacteria.
- Defective colon mucus, allowing bacterial penetration, is observed in mouse colitis models and active UC patients.
- Modulation of colon mucus properties offers a novel perspective on UC pathophysiology.
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