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.
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.
Authors: N Borruel; M Carol; F Casellas; M Antolín; F de Lara; E Espín; J Naval; F Guarner; J R Malagelada Journal: Gut Date: 2002-11 Impact factor: 23.059
Authors: Dov Wengrower; Giuliana Zanninelli; Giovanni Latella; Stefano Necozione; Issa Metanes; Eran Israeli; Joseph Lysy; Mark Pines; Orit Papo; Eran Goldin Journal: Can J Gastroenterol Date: 2012-01 Impact factor: 3.522
Authors: Y Okada; Y Tsuzuki; J Miyazaki; K Matsuzaki; R Hokari; S Komoto; S Kato; A Kawaguchi; S Nagao; K Itoh; T Watanabe; S Miura Journal: Gut Date: 2005-11-18 Impact factor: 23.059
Authors: Mathias Chamaillard; Dana Philpott; Stephen E Girardin; Habib Zouali; Suzanne Lesage; Fabrice Chareyre; The Hung Bui; Marco Giovannini; Ulrich Zaehringer; Virginie Penard-Lacronique; Philippe J Sansonetti; Jean-Pierre Hugot; Gilles Thomas Journal: Proc Natl Acad Sci U S A Date: 2003-03-07 Impact factor: 11.205