COLONIC INFLAMMATION

Comparative study of the intestinal mucus barrier in normal and inflamed colon

Alexander Swidsinski¹, Vera Loening-Baucke¹, Franz Theissig⁴, Holger Engelhardt⁵, Stig Bengmark⁶, Stefan Koch⁴, Herbert Lochs², Yvonne Dörffel³

¹ Charite Hospital, Humboldt University, CCM, Laboratory for Molecular Genetics, Polymicrobial Infections and Bacterial Biofilms, Berlin, Germany
² Department of Medicine, Section of Gastroenterology, Hepatology and Endocrinology, Humboldt University, Charite Hospital, CCM, Berlin, Germany
³ Poliklinik, Luisenstr, Charité, Humboldt University Berlin, CCM, Berlin, Germany
⁴ Institute of Pathology, Humaine Klinikum Bad Saarow/Fürstenwalde, Pieskower Strasse, Bad Saarow, Germany
⁵ Department for General, Visceral and Thoracic Surgery, Humaine Klinikum Bad Saarow/Fürstenwalde, Pieskower Strasse, Bad Saarow, Germany
⁶ UCL Institute of Hepatology University College, London Medical School, Chenies Mews, London, UK

Correspondence to:
Dr A Swidsinski
Humboldt University, Charité, CCM, 10098 Berlin, Germany; alexander.swidsinski{at}charite.de

Aim: To study the role of mucus in the spatial separation of intestinal bacteria from mucosa.

Patients and methods: Mucus barrier characteristics were evaluated using histological material obtained by biopsy from purged colon, colon prepared with enema and material from untreated appendices fixed with non-aqueous Carnoy solution. Bacteria were evaluated using fluorescence in situ hybridization, with bacterial 16S RNA probes and related to the periodic acid Schiff alcian blue stain. Biopsies from controls (n = 20), patients with self-limiting colitis (SLC; n = 20), ulcerative colitis (n = 20) and 60 randomly selected appendices were investigated.

Results: The mucosal surface beneath the mucus layer was free of bacteria in 80% of the normal appendices and biopsies from controls. The thickness of the mucus layer and its spread decreased with increasing severity of the inflammation; the epithelial surface showed bacterial adherence, epithelial tissue defects and deep mucosal infiltration with bacteria and leucocytes. Bacteria and leucocytes were found within mucus in all biopsy specimens from patients with ulcerative colitis, SLC, and acute appendicitis. The concentration of bacteria within mucus was inversely correlated to the numbers of leucocytes.

Conclusions: The large bowel mucus layer effectively prevents contact between the highly concentrated luminal bacteria and the epithelial cells in all parts of the normal colon. Colonic inflammation is always accompanied by breaks in the mucus barrier. Although the inflammatory response gradually reduces the number of bacteria in mucus and faeces, the inflammation itself is not capable of preventing bacterial migration, adherence to and invasion of the mucosa.

Abbreviations: DAPI, 4,6-diamidino-2-phenylindole, a usual DNA stain; FISH, fluorescence in situ hybridization; FITC, fluorescein isothiocyanate; IBD, inflammatory bowel disease; PAS, periodic acid Schiff; SLC, self-limiting colitis

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