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Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis
  1. Malin E V Johansson1,
  2. Jenny K Gustafsson1,
  3. Jessica Holmén-Larsson1,
  4. Karolina S Jabbar1,
  5. Lijun Xia2,
  6. Hua Xu3,
  7. Fayez K Ghishan3,
  8. Frederic A Carvalho4,
  9. Andrew T Gewirtz4,
  10. Henrik Sjövall5,
  11. Gunnar C Hansson1
  1. 1Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden
  2. 2Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  3. 3Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, Arizona, USA
  4. 4Department of Biology, Georgia State University, Atlanta, Georgia, USA
  5. 5Department Internal Medicine, University of Gothenburg, Gothenburg, Sweden
  1. Correspondence to Dr Gunnar C Hansson, Department of Medical Biochemistry, University of Gothenburg, Box 440, Gothenburg 405 30, Sweden; gunnar.hansson{at}medkem.gu.se

Abstract

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.

  • MUCUS
  • MUCINS
  • MUCOSAL BARRIER
  • MUCOSAL PATHOLOGY
  • BACTERIAL TRANSLOCATION

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

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