Derangement of mucosal barrier function by bacteria colonizing the rat colonic mucosa

Abstract

Interaction between gut flora and the intestinal barrier may involve changes in permeability. Rats with a colonic segment excluded from faecal transit were surgically prepared. Matched groups were either kept on luminal antibiotics to prevent colonization of the segment or recolonized with mixed rat flora. Permeability to low-dose trinitrobenzenesulphonic acid (TNBS) or trinitrophenol (TNP), and mucosal injury by the compounds at a high dose were tested in antibiotic and recolonized rats (the compounds differ in water solubility but share a common antigenic domain). Lumen to blood clearance of the hydrophilic probe (TNBS) was faster in recolonized than in antibiotic rats. The hydrophobic compound TNP was absorbed at faster rates than TNBS, but there was no difference between antibiotic and recolonized rats. Instillation of TNBS at a high dose induced mucosal release of inflammatory mediators and tissue myeloperoxidase accumulation in recolonized rats but not in antibiotic rats. Large necrotic lesions with submucosal involvement after TNBS were only observed in recolonized rats. In contrast, TNP induced mucosal inflammation and large lesions with submucosal necrosis both in recolonized and in antibiotic rats. Colonizing bacteria may increase intestinal permeability to hydrophilic compounds and render the mucosa susceptible to injury.