Stimulation of transforming growth factor beta1 by enteric bacteria in the pathogenesis of rat intestinal fibrosis.
OBJECTIVE
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.
Mourelle
M
M
Digestive System Research Unit, Hospital General Vall d'Hebron, Barcelona, Spain.
Salas
A
A
Guarner
F
F
Crespo
E
E
García-Lafuente
A
A
Malagelada
J R
JR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000472:pathogenicity*; D003092:Colitis / Q000097:blood; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis; D007415:Intestinal Obstruction / Q000209:etiology*; D007422:Intestines / Q000382:microbiology* / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D016212:Transforming Growth Factor beta; D003094:Collagen