Ischaemia-induced mucus barrier loss and bacterial penetration are rapidly counteracted by increased goblet cell secretory activity in human and rat colon

Gut. 2013 Feb;62(2):250-8. doi: 10.1136/gutjnl-2011-301956. Epub 2012 May 25.


Objective: Colonic ischaemia is frequently observed in clinical practice. This study provides a novel insight into the pathophysiology of colon ischaemia/reperfusion (IR) using a newly developed human and rat experimental model.

Design: In 10 patients a small part of colon that had to be removed for surgical reasons was isolated and exposed to 60 min of ischaemia (60I) with/without different periods of reperfusion (30R and 60R). Tissue not exposed to IR served as control. In rats, colon was exposed to 60I, 60I/30R, 60I/120R or 60I/240R (n=7 per group). The tissue was snap-frozen or fixed in glutaraldehyde, formalin or methacarn fixative. Mucins were stained with Periodic Acid Schiff/Alcian Blue (PAS/AB) and MUC2/Dolichos biflorus agglutinin (DBA). Bacteria were studied using electron microscopy (EM) and fluorescent in situ hybridisation (FISH). Neutrophils were studied using myeloperoxidase staining. qPCR was performed for MUC2, interleukin (IL)-6, IL-1β and tumour necrosis factor α.

Results: In rats, PAS/AB and MUC2/DBA staining revealed mucus layer detachment at ischaemia which was accompanied by bacterial penetration (in EM and FISH). Human and rat studies showed that, simultaneously, goblet cell secretory activity increased. This was associated with expulsion of bacteria from the crypts and restoration of the mucus layer at 240 min of reperfusion. Inflammation was limited to minor influx of neutrophils and increased expression of proinflammatory cytokines during reperfusion.

Conclusions: Colonic ischaemia leads to disruption of the mucus layer facilitating bacterial penetration. This is rapidly counteracted by increased secretory activity of goblet cells, leading to expulsion of bacteria from the crypts as well as restoration of the mucus barrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis, Ischemic / metabolism*
  • Colitis, Ischemic / microbiology
  • Colon / blood supply*
  • Cytokines / metabolism
  • Fluorescent Antibody Technique
  • Goblet Cells / metabolism*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Inflammation / metabolism
  • Inflammation / pathology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Male
  • Mucin-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / microbiology


  • Cytokines
  • MUC2 protein, human
  • Muc2 protein, rat
  • Mucin-2