Various studies suggest that gut microbial dysbiosis may be related to some disorders such as inflammatory bowel disease (IBD), gastrointestinal cancers, diabetes, obesity, hypertension, renal disorders and etc [6, 18]. Association between gut microbiota and CRC has been reported in several studies [5-8, 19]. According to previous reports, bacterial species including Streptococcus species, H. pylori, E. faecalis, B. fragilis, C. septicum and E. coli have a role in the occurrence and progression of CRC . B. fragilis is the most frequent anaerobe isolated in clinical cases of diarrhea, peritonitis, intra-abdominal abscesses and sepsis . It is also associated with intestinal tumors due to enterotoxin production . It has been proposed that enterotoxigenic B. fragilis may act as “keystone” pathogen that facilitate the establishment of dysbiotic microbial communities and induce CRC [6, 20, 21]. In the present study, the frequency of enterotoxigenic B. fragilis in stool samples of CRC patients was compared with healthy controls. According to neu gene determination, B. fragilis was detected more frequently from stool samples of CRC patients than from the matched controls (58.3% and 26.6%, respectively; P< 0.05). In previous study from Iran, higher numbers of F. nucleatum, E. feacalis, S. bovis, ETBF and Porphyromonas spp. were detected in adenomatous polyp cases, consisting tubular adenoma and especially villous/ tubuvillous polyp, in contrast to samples from the normal groups (P < 0.001) . It is reported that over time accumulation of ETBF strains in colonic epithelial crypts may enhance carcinogenesis .
In our study, the rate of bft gene in CRC cases was significantly higher than in controls (P<0.05). This result supports prior works where bft detection in stool and colon mucosal samples were significantly higher in CRC patients than in outpatient controls [8, 14]. According to Boleij et al study, the mucosa of CRC patients was significantly more often bft-positive on left (85.7%) and right (91.7%) tumor compared with left and right control biopsies (53.1%; P = .033 and 55.5%; P = .04, respectively) . It is assumed that BFT exposure in the human colon may induces rapid onset of chronic IL-17–dependent inflammation, oxidative DNA damage, epithelial barrier damage and activation of STAT3/Th17 immune responses yielding to increased risk of CRC [3, 6, 10, 19].
The presence of bft gene in CRC patients stage III was significantly higher than stages I and II (P< 0.05). According to Boleij et al and Viljoen et al studies, bft was detected in the majority of CRC patients in particular with late-stage disease, possibly due to enhanced anaerobiosis on larger tumors [11, 14].
Furthermore, the frequency of bft-2 isotype in CRC cases was significantly higher than healthy control group (P<0.05). Similar to our study, Boleij et al show bft-2 as the most common mucosal isotype of B. fragilis . According to in vitro and in vivo surveys, BFT-2 has greater potency and biological activity compared to BFT-1 and exhibites enhanced carcinogenic potential . However, in study conducted by Ulger Toprak et al, bft-1 was detected more than bft-2 in stool samples of colon cancer patients and control group. The bft-1 isotype was also found in all isolates of extraintestinal sites in their study . Also, bft-1 isotype was the most frequent allele among ETBF strains isolated from diarrheal diseases [14, 22].
One of the limitations of the present study was the small size of CRC group. Furthermore, data regarding environmental factors and some clinicopathological and demographic characteristics that may contribute to carcinogenesis were not collected from CRC patients in our study.