Abstract
BackgroundEnterotoxigenic Bacteroides fragilis (ETBF) is a toxin-producing bacteria thought to possibly promote colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. Here, we aim to examine the association of colonic mucosal colonization with ETBF and the presence of a range of lesions on the colonic neoplastic spectrum.MethodsMucosal tissue from up to four different colonic sites was obtained from a consecutive series of 150 patients referred for colonoscopy. The presence and relative abundance of the B. fragilis toxin gene (bft) in each tissue sample was determined using quantitative PCR, and associations with clinicopathological characteristics were analysed.FindingsWe found a high concordance of ETBF between different colonic sites (86%). Univariate analysis showed statistically significant associations between ETBF positivity and the presence of low-grade dysplasia (LGD), tubular adenomas (TA), and serrated polyps (P-values of 0.007, 0.027, and 0.007, respectively). A higher relative abundance of ETBF was significantly associated with LGD and TA (P-values of < 0.0001 and 0.025, respectively). Increased ETBF positivity and abundance was also associated with left-sided biopsies, compared to those from the right side of the colon.ConclusionOur results showing association of ETBF positivity and increased abundance with early-stage carcinogenic lesions underlines its importance in the development of colorectal cancer, and we suggest that detection of ETBF may be a potential marker of early colorectal carcinogenesis.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide, with approximately 1.4 million new cases diagnosed in 2012[1]
Our results showing association of Enterotoxigenic Bacteroides fragilis (ETBF) positivity and increased abundance with earlystage carcinogenic lesions underlines its importance in the development of colorectal cancer, and we suggest that detection of ETBF may be a potential marker of early colorectal carcinogenesis
It has been proposed that certain bacterial species, such as enterotoxigenic B. fragilis (ETBF), may act as “keystone” or “driver” pathogens that facilitate the establishment of dysbiotic microbial communities and induce CRC [21, 22]
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide, with approximately 1.4 million new cases diagnosed in 2012[1]. Current thinking on carcinogenesis hypothesizes that cancer originates from a sequence of events that include a pathogenic stimulus, e.g. bacterial infection, followed by chronic inflammation, which in turn leads to changes in the cellular microenvironment, resulting in precancerous and cancerous changes [3]. If this hypothesis is correct, the majority of reported genetic findings in cancer are late events or epiphenomena that occur after the precancerous stage. We aim to examine the association of colonic mucosal colonization with ETBF and the presence of a range of lesions on the colonic neoplastic spectrum
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