Modulation of colonic barrier function by the composition of the commensal flora in the rat.

Abstract

Background and aims--Altered intestinal permeability is a key pathogenetic factor of idiopathic bowel inflammation. We investigated in the rat if changes in the composition of the bowel flora can alter colonic permeability.

Methods--A colonic segment was surgically excluded from faecal transit and brought out as a loop to the abdominal wall through two colostomies. The loop was used for colonisation with specific bacterial strains after eradication of the native flora with antibiotics. Lumen to blood clearance of dextran (molecular weight 70 000) and mannitol (molecular weight 182) was measured in rats recolonised with a single bacterial strain from rat colonic origin, and in control rats whose colonic loop was kept free of bacteria by antibiotics. Actual colonisation was confirmed by culture of segment effluents. Results--Colonisation with Escherichia coil, Klebsiella pneumoniae, and Streptococcus viridans significantly increased lumen to blood clearance of mannitol. Colonisation with Lactobacilus brevis had the opposite effect and reduced permeability to mannitol. Bacteroides fragilis did not induce significant changes. Permeability to dextran was not altered by any of the strains tested.

Conclusions--Certain commensal bacteria can modify colonic wall permeability to luminal substances.

(Gut 2001;48:503-507)

Keywords: bacteria; dextran; intestinal permeability; mannitol; rat

The colonic mucosal barrier is a complex physicochemical structure that separates the internal "milieu" from a polluted luminal environment. Barrier function ultimately depends on the integrity of the mucosa--from the endothelium to the epithelial cell lining--and the reactivity of dynamic defensive factors such as mucosal blood flow and epithelial secretions. A gel formed by the interaction of various mucosal secretions, including mucin glycoproteins, trefoil peptides, and surfactant phospholipids, comprises the mucus layer that covers the epithelium. [1-3] This layer gives hydrophobic properties to the surface and prevents the influx of water soluble bacterial products and toxins. [4] A large variety of bacterial populations with different pathogenic potentials and a high concentration of chemical and bacterial toxins are constantly challenging the structure and function of the colonic mucosal barrier.

Morphological or functional derangement of the mucosal barrier may lead to changes in intestinal permeability. Clinical studies have shown altered intestinal permeability in a number of disorders, including intestinal infections, Crohn's disease, coeliac sprue, food intolerance, and non-steroidal anti-inflammatory drug induced enteropathy. [5] Increased intestinal permeability has also been observed in relatives of patients with Crohn's disease [6] and in patients in remission. [7] These observations led to a proposal that the permeability defect may be a key pathogenetic factor of idiopathic bowel inflammation as it facilitates mucosal penetration of proinflammatory antigens that challenge the immune system. In several conditions, including Crohn's disease, ulcerative colitis, and coeliac disease, mucosal overproduction of immunoglobulin G antibodies reflects a state of hyperresponsiveness to usually harmless luminal antigens. [8] [9]

Previous experimental work from our laboratory showed that…