Enterotoxigenic bacteroides fragilis: a potential instigator of colitis.
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.
Rabizadeh
Shervin
S
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Rhee
Ki-Jong
KJ
Wu
Shaoguang
S
Huso
David
D
Gan
Christine M
CM
Golub
Jonathan E
JE
Wu
XinQun
X
Zhang
Ming
M
Sears
Cynthia L
CL
D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000633:toxicity; D001441:Bacteroides fragilis / Q000302:isolation & purification / Q000378:metabolism*; D001835:Body Weight; D002432:Cecum / Q000473:pathology; D003092:Colitis / Q000139:chemically induced* / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004768:Enterotoxins / Q000096:biosynthesis* / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D001426:Bacterial Proteins; D004768:Enterotoxins; D016264:Dextran Sulfate