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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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