Enterotoxigenic Bacteroides fragilis: A Possible Etiological Candidate for Bacterially-Induced Colorectal Precancerous and Cancerous Lesions

Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) produces Bacteroides fragilis toxin (BFT), which is associated with acute diarrheal, inflammatory bowel disease, and colorectal cancer (CRC). In experimental models, ETBF has been shown to contribute to colon carcinogenesis. The present study was conducted to investigate mucosal colonization of ETBF in the colon to find a possible association between the presence of ETBF and precancerous and cancerous lesions. The mucosal biopsies of involved sites were obtained from 68 patients with precancerous and cancerous lesions and 52 healthy controls (HC). The samples were cultured on Bacteroides Bile Esculin agar. Then, specific primers were designed to detect B. fragilis and bft gene using quantitative real-time PCR, and the possible links of ETBF with clinicopathological characteristics was evaluated. Also real-time PCR was performed to detect the bft gene subtypes. Bacteroides fragilis was detected in 51% of the patients and 48% of HCs cultures. The 16SrRNA gene was found to be present in 63 and 81% of the patients and HCs' samples, respectively. Moreover, the bft gene was detected in 47 and 3.8% of the patients and HCs, respectively. Also, B. fragilis was significantly more abundant in the patients' samples compared to those of HCs. In the patient group, higher odds ratio (OR) of ETBF was significantly associated with serrated lesions and adenoma with low-grade dysplasia. The bft1 gene was the most prevalent subtype of bft gene, followed by the bft2 gene. This was the first study in Iran to demonstrate increased positivity of ETBF in patients with precancerous and cancerous lesions. In this study, the bft gene was found to be associated with CRC, especially in the patients with precancerous lesions and initial carcinogenic lesions. Moreover, the results suggest that mucosal BFT exposure is common and could be a risk factor and a screening marker for developing CRC.

WITHDRAWN: Fecal Enterotoxigenic Bacteroides fragilis-Peptostreptococcus stomatis-Parvimonas micra Biomarker for Noninvasive Diagnosis and Prognosis of Colorectal Laterally Spreading Tumor

“…ETBF has been known as a contributor to chronic colonic diseases, including oncogenic transformation, intestinal in ammation, chronic colonic dysfunctions and colorectal precancerous and cancerous lesions (24)(25)(26)(27)(28). Combined action of the ETBF and IL-17 on colonic epithelial cells promoted the differentiation of monocytic-myeloid-derived suppressor cells(MO-MDSCs) and suppressed T-cell proliferation (27).…”

The effect of immunoregulatory bacteria on the transcriptional activity of Foxp3 and RORyt genes in the gut-associated lymphoid tissue with Salmonella-induced inflammation in the presence of vancomycin and Ваcteroides fragilis

“…At the same time, there are recent data indicated that enterotoxigenic B. fragilis strains (ETBF) producing B. fragilis toxin (BFT) are associated with CRC, especially in the patients with precancerous lesions and initial carcinogenic lesions ( 40 ) and with ulcerative colitis, especially in the patients with diarrhea symptoms ( 41 ). Furthermore, some studies have been published recently, describing ETBF as a trigger for chronic Stat3/IL-17-driven colitis which is IL-17 dependent and induces T17 colitis and tumorogenesis through the secretion of the metalloproteinase Bft and other associated factors ( 42 ).…”

Pulmonary Micro-Ecological Changes and Potential Microbial Markers in Lung Cancer Patients

“…Moreover, enterotoxigenic Bacteroides fragilis and B . fragilis toxin gene was upregulated in patients with precancerous and cancerous lesions ( 67 ). Besides, microbial fermentation may have negative consequences owing to the generation of potentially toxic and cancer-promoting metabolites, such as ammonia, amines, phenols, sulphides, and nitrosamines ( 68 ).…”