Stimulation of transforming growth factor beta1 by enteric bacteria in the pathogenesis of rat intestinal fibrosis

Gastroenterology. 1998 Mar;114(3):519-26. doi: 10.1016/s0016-5085(98)70535-9.


Background & aims: Bacteria and their products stimulate inflammatory responses. Certain mediators, such as transforming growth factor beta1 (TGF-beta1), induce collagen synthesis. Excess collagen deposition results in bowel strictures. The aim of this study was to investigate the role of bacteria and TGF-beta1 in the pathogenesis of intestinal fibrosis.

Methods: In rats with colitis, the effects of bowel decontamination with antibiotics on TGF-beta1, tumor necrosis factor alpha (TNF-alpha), 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-beta1 on tissue collagen deposition was studied.

Results: Rats with chronic colitis showed increased levels of TGF-beta1, TNF-alpha, and collagen in the tissue and a high rate of bowel strictures. Antibiotic treatment significantly prevented the increase in TGF-beta1 and collagen and the formation of strictures. Inoculation of bacterial suspensions into the colonic wall increased tissue TGF-beta1 and collagen content. Neutralizing antibody to TGF-beta1 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-beta1 and induce deposition of collagen in the colonic wall.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / pathogenicity*
  • Colitis / blood
  • Collagen / metabolism
  • Fibrosis
  • Intestinal Obstruction / etiology*
  • Intestines / microbiology*
  • Intestines / pathology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta / biosynthesis*


  • Anti-Bacterial Agents
  • Transforming Growth Factor beta
  • Collagen