Enterotoxigenic Bacteroides fragilis: A potential instigator of colitis

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Original Article

Enterotoxigenic Bacteroides fragilis: A potential instigator of colitis

Shervin Rabizadeh, MD, MBA 1 *, Ki-Jong Rhee, PhD 2, Shaoguang Wu, MD 2, Huso, DVM, PhD 3, M. Gan, PhD 4 5, E. Golub, PhD, MPH 2, XinQun Wu, MD 2, Ming Zhang, MS 2, L. Sears, MD 2 4 5

1Department of Pediatrics, s Hopkins University School of Medicine, Baltimore, land2Department of Medicine, s Hopkins University School of Medicine, Baltimore, land3Department of Comparative Medicine, s Hopkins University School of Medicine, Baltimore, land4Department of Oncology, s Hopkins University School of Medicine, Baltimore, land5Sidney Kimmel Comprehensive Cancer Center, s Hopkins University School of Medicine, Baltimore, land

email: Shervin Rabizadeh (srabiza1@...)

*Correspondence to Shervin Rabizadeh, 600 North Wolfe St., Brady 320, Baltimore, MD 21287

Funded by: Crohn's and Colitis Foundation through a Senior Investigator Award; Grant Number: RO1 DK45496 SPORE; Grant Number: CA62924, R24 DK64388, RR00171 NCI Division of Cancer Prevention Contract; Grant Number: HHSN261200433002C Institutional Training for Pediatricians; Grant Number: 5 T32 HD44355

Keywords

enterotoxigenic Bacteroides fragilis (ETBF) • colitis • dextran sodium sulfate (DSS)

Abstract

Background: Inflammatory bowel disease (IBD) is proposed to result from a dysregulated mucosal immune response to the colonic flora in genetically susceptible individuals. Enterotoxigenic Bacteroides fragilis (ETBF), a molecular subclass of the common human commensal, B. fragilis, has been associated with IBD. This study investigated whether ETBF colonization of mice initiated colitis or modified the clinical course of a colitis agonist, dextran sodium sulfate (DSS).

Methods: Four- and 6-week-old C57BL/6 mice were inoculated with buffer, nontoxigenic B. fragilis (NTBF) strain 9343(pFD340), or ETBF strain 86-5443-2-2 via orogastric tube. A subset of mice received 2% DSS several days pre- or post-inoculation of bacteria. Clinical status was assessed throughout the experiment and severity of colonic inflammation was scored after sacrifice.

Results: All mice, including those receiving DSS, were clinically well prior to bacterial inoculation. NTBF and ETBF colonization was similar. Regardless of mouse age or timing of DSS administration, mice who received ETBF+DSS experienced worse colitis reflected by less weight gain, enhanced gross disease, and greater inflammation in their colons (P < 0.05), especially in the cecum. In particular, younger mice had more extensive disease. Mice inoculated only with ETBF also exhibited colitis with more severe inflammation when compared to all other groups (P < 0.05) except the ETBF+DSS group.

Conclusions: ETBF, a colonic commensal, alone stimulates colitis and significantly enhances colonic inflammation in DSS-treated mice. This study suggests that acquisition of ETBF colonization may be a potential factor in initiation and/or exacerbation of colitis.

(Inflamm Bowel Dis 2007)

Received: 20 July 2007; Accepted: 30 July 2007

Digital Object Identifier (DOI)