The association between fecal enterotoxigenic B. fragilis with colorectal cancer

Abstract

Background: Enterotoxigenic Bacteroides fragilis (ETBF) is an enterotoxin-producing bacterium that possibily has a role in the occurrence and progression of colorectal cancer (CRC) by modulating the mucosal immune response and inducing epithelial cell changes. The aim of this study was to investigate the frequency of ETBF in stool samples of CRC patients and healthy volunteers. Methods: A total of 60 stool samples from confirmed CRC patients and 60 stool samples from healthy volunteers with no personal or familial history or diagnosis of colorectal disease were collected. Stool samples were screened for direct detection of B. fragilis using PCR targeting the marker genes of neu and bft. Enterotoxin isotypes bft-1, bft-2 and bft-3 were also detected in B. fragilis positive samples. Results: The frequency of B. fragilis among CRC and control cases was 58.3 and 26.6%, respectively (P < 0.05). The rate of bft gene in CRC cases was significantly higher than in controls (P < 0.05). Also, the presence of bft gene in CRC patients stage III was significantly higher than stages I and II (P < 0.05). Enterotoxin isotype bft-2 was detected with higher frequency among CRC patients than healthy control (P < 0.05). Conclusion: Our results show the association between fecal ETBF and CRC, and we suggest that detection of ETBF may be a potential marker for colorectal cancer diagnosis. However, additional investigations on tumor and paired normal tissue samples are required to substantiate this possible correlation.

Fusobacterium nucleatum Accelerates the Progression of Colitis-Associated Colorectal Cancer by Promoting EMT

“…With advances in sequencing techniques, studies have reported correlations between microbiota dysbiosis and CRC, and pathogenic microbiota that accelerate colon cancer progression have been identified [ 10 ]. For example, it has been reported that the enterotoxigenic Bacteroides fragilis contribute to colon carcinogenesis by producing toxins [ 11 ]. Together with numerous potential carcinogenic intestinal microorganisms, Fusobacterium nucleatum ( F. nucleatum ) has been reported to be a contributing factor to CRC progression based on its presence in CRC specimens [ 12 , 13 , 14 ].…”

Influence of Iron on the Gut Microbiota in Colorectal Cancer

“…In a study by Boleij et al, 72.7% of early-stage colorectal tumors had a bft gene present, while 100% of late-stage tumors had a bft gene present [68]. This supports the role of enterotoxigenic Bacteroides fragilis in the progression of colorectal cancer, as late-stage tumors have more carcinogenic bacterial toxin Along with this, the abundance of enterotoxigenic Bacteroides fragilis in colorectal mucosa has been shown to be an independent predictor of three-year survival [69,71]. This supports the potential role of enterotoxic Bacteroides fragilis as both a driver and pathogenic passenger bacterium in colorectal carcinogenesis [34].…”

“…Enterotoxigenic Bacteroides fragilis is a pathogenic bacterium that produces the enterotoxin Bacteroides fragilis toxin (bft) and is associated with colorectal cancer initiation and progression [68]. This occurs through modulation of the mucosal immune system and inducing alterations in epithelial cells, leading to a compromised colonic barrier [57,69]. Enterotoxic Bacteroides fragilis has been associated with colonic pre-neoplastic lesions and has been suggested to be a potential biomarker for early detection of colorectal carcinogenesis [70].…”

Gut Microbiota and Colon Cancer: A Role for Bacterial Protein Toxins?

“…The first study demonstrating an increased prevalence of ETBF in the stool specimens of CRC patients (38%) compared with the control group (12%) was conducted by Ulger Toprak and coworkers [ 95 ]. Different reports have shown an association between bft gene and CRC, particularly in the late stage (III/IV) of CRC [ 96 , 97 , 98 , 99 ] and significant associations of ETBF with tubular adenomas, serrated lesions, and low-grade dysplasia [ 100 ]. Interestingly, patchy bacterial biofilms composed predominately of E. coli and B. fragilis were identified in the colonic mucosa of patients with FAP, who develop benign precursor lesions (polyps) early in life.…”