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

Abstract

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.A ccepted hypotheses for the aetiology of inflammatory bowel disease (IBD) suggest that contact between intestinal bacteria and mucosal surfaces triggers and perpetuates the colonic inflammation.

Stress‐induced host membrane remodeling protects from infection by non‐motile bacterial pathogens

“…In addition to bacterial pathogen infection, this mechanism might also be relevant to restrict commensal bacteria translocation through the intestinal epithelium. Given that the mucus layer is reduced during inflammation (Swidsinski et al , 2007) and thus more bacteria are probing the epithelial surface, it is conceivable that the depletion of membrane rafts limits the docking of such bacteria and their potential translocation through the intestinal barrier. Indeed, commensal bacteria have been shown to exploit membrane raft‐mediated transcellular pathways to cross the intestinal epithelium, in mechanisms dependent (Kalischuk et al , 2009) or independent (Clark et al , 2005) of co‐infection with bacterial pathogens.…”

Quantification by computerized morphometry of tissue levels of sulfomucins and sialomucins in diversion colitis in rats

“…In addition to providing mechanical protection, they present bactericide properties 7,8 . Breakage of the protective barrier or mucus, as occurs in inflammatory intestinal diseases, allows invasion of bacteria through the epithelial surface 7,8,19 .…”

“…This experimental model was chosen because we believed that intestinal diversion through the use of loop colostomies would not ensure complete exclusion of the fecal stream 6 . With the aim of ensuring that the experimental model adopted would be capable of causing inflammation to appear in the colon mucosa of the segments excluded from the transit, we preferred to use an inflammation grading scale that had previously been validated 19 . This allowed the main histological changes encountered to be considered together 19,35 .…”

“…With the aim of ensuring that the experimental model adopted would be capable of causing inflammation to appear in the colon mucosa of the segments excluded from the transit, we preferred to use an inflammation grading scale that had previously been validated 19 . This allowed the main histological changes encountered to be considered together 19,35 . The results showed that in the segments excluded from the fecal stream, there was a greater degree of inflammation than in the segments with transit preserved, independent of the duration of exclusion.…”

Morphometric Features and Glycoconjugate Pattern of Rabbit Intestine are Affected by Particle Size of Pelleted Diets

“…Alterations in the intestinal mucus layer have been reported in various intestinal disorders (Shirazi et al, 2000;Einerhand et al, 2002;Swidsinski et al, 2007). Reduced mucus thickness, altered glycosylation, and decreased sulfation together with depleted goblet cells have been reported in inflammatory bowel disease and ulcerative colitis (Badr-el-Din et al, 1988;Einerhand et al, 2002).…”