The human body comprises fewer host cells than bacterial cells, most of which are obligate anaerobes residing in the gut. The symbiont Bacteroides fragilis constitutes a relatively small proportion (up to 1%–2%) of cultured fecal bacteria, but colonizes most humans. There are 2 classes of B. fragilis distinguished by their ability to secrete a zinc-dependent metalloprotease toxin, B. fragilis toxin (BFT). Strains that do not secrete BFT are nontoxigenic B. fragilis (NTBF), and those that do are called enterotoxigenic B. fragilis (ETBF). ETBF can induce clinical pathology, including inflammatory diarrhea, although asymptomatic colonization may be common. Intestinal inflammation is mediated by BFT, as yet the only known virulence factor of ETBF. Recent experimental evidence demonstrating that ETBF-driven colitis promotes colon tumorigenesis has generated interest in the potential contribution of ETBF to human colon carcinogenesis. Critical questions about the epidemiology of chronic, subclinical human colonization with ETBF and its impact on the biology of the colon need to be addressed.
(A) ETBF induces marked gross tumorigenesis in the distal colon of Min mice 3 months after inoculation of ETBF or buffer (sham). (B) Mouse colonization by a single inoculation of ETBF rapidly induces mucosal IL-17 production that persists for up to 1 year during ongoing subclinical ETBF colonization of mice. In Min mice, excess colon adenoma initiation is detectable histologically by 1 week after onset of ETBF colonization, with visible excess tumor formation apparent after 4 or more weeks of ETBF colonization. IL-17 neutralization inhibits ETBF colon tumor formation. Thus, the ETBF murine model provides an accelerated IL-17–dependent inflammatory colon cancer model potentially helpful for understanding mechanisms of human colon carcinogenesis.