Stimulation of transforming growth factor β1 by enteric bacteria in the pathogenesis of rat intestinal fibrosis

Background & Aims: Bacteria and their products stimulate inflammatory responses. Certain mediators, such as transforming growth factor β1 (TGF-β1), induce collagen synthesis. Excess collagen deposition results in bowel strictures. The aim of this study was to investigate the role of bacteria and TGF-β1 in the pathogenesis of intestinal fibrosis. Methods: In rats with colitis, the effects of bowel decontamination with antibiotics on TGF-β1, tumor necrosis factor α (TNF-α), and collagen content in colonic tissue were studied. In normal rats, bacteria of the predominant flora were inoculated into the colonic wall. The effect of neutralizing antibody to TGF-β1 on tissue collagen deposition was studied. Results: Rats with chronic colitis showed increased levels of TGF-β1, TNF-α, and collagen in the tissue and a high rate of bowel strictures. Antibiotic treatment significantly prevented the increase in TGF-β1 and collagen and the formation of strictures. Inoculation of bacterial suspensions into the colonic wall increased tissue TGF-β1 and collagen content. Neutralizing antibody to TGF-β1 prevented collagen deposition. Colonic wall inoculations with single anaerobic strains (Clostridium ramosum, Bacteroides fragilis, and Bacteroides uniformis), but not with aerobes, induced collagen deposition. Conclusions: Certain strains of the common flora stimulate TGF-β1 and induce deposition of collagen in the colonic wall.GASTROENTEROLOGY 1998;114:519-526