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Infection and Immunity, April 2001, p. 2277-2285, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2277-2285.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Different Subsets of Enteric Bacteria Induce and Perpetuate Experimental Colitis in Rats and Mice

Heiko C. Rath,1,2 Michael Schultz,1,2 René Freitag,2 Levinus A. Dieleman,1 Fengling Li,1 Hans-Jörg Linde,3 Jürgen Schölmerich,2 and R. Balfour Sartor1,*

Center for GI Biology and Disease, University of North Carolina, Chapel Hill, North Carolina,1 and Department of Internal Medicine I2 and Institute of Medical Microbiology and Hygiene,3 University of Regensburg, Regensburg, Germany

Received 18 September 2000/Returned for modification 2 November 2000/Accepted 28 December 2000

Resident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem before or after receiving 5% dextran sodium sulfate (DSS). Germfree transgenic rats were colonized with specific-pathogen-free enteric bacteria grown overnight either in anaerobic or aerobic atmospheres. Nontransgenic rats colonized with anaerobic bacteria served as negative controls. Although preventive metronidazole significantly attenuated colitis in transgenic rats and DSS-treated mice, it had no therapeutic benefit once colitis was established. Ciprofloxacin also partially prevented but did not treat colitis in B27 transgenic rats. In both animal models vancomycin-imipenem most effectively prevented and treated colitis. Germfree transgenic rats reconstituted with enteric bacteria grown under anaerobic conditions had more aggressive colitis than those associated with aerobic bacteria. These results suggest that a subset of resident luminal bacteria induces colitis, but that a complex interaction of commensal aerobic and anaerobic bacteria provides the constant antigenic drive for chronic immune-mediated colonic inflammation.

* Corresponding author. Mailing address: Division of Digestive Diseases, CB#7038, Room 032A Glaxo Bldg., University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7038. Phone: (919) 966-0149. Fax: (919) 966-7468. E-mail: rbs{at}med.unc.edu.

Infection and Immunity, April 2001, p. 2277-2285, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2277-2285.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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