Skip to main content
Top
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Polymerase Chain Reaction | Research article

The association between fecal enterotoxigenic B. fragilis with colorectal cancer

Authors: Fakhri Haghi, Elshan Goli, Bahman Mirzaei, Habib Zeighami

Published in: BMC Cancer | Issue 1/2019

Login to get access

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.
Literature
2.
go back to reference Liu C-J, Zhang Y-L, Shang Y, Wu B, Yang E, Luo Y-Y, Li X-R. Intestinal bacteria detected in cancer and adjacent tissue from patients with colorectal cancer. Oncol Lett. 2019;17(1):1115–27.PubMed Liu C-J, Zhang Y-L, Shang Y, Wu B, Yang E, Luo Y-Y, Li X-R. Intestinal bacteria detected in cancer and adjacent tissue from patients with colorectal cancer. Oncol Lett. 2019;17(1):1115–27.PubMed
4.
go back to reference Jahani-Sherafat S, Alebouyeh M, Moghim S, Ahmadi Amoli H, Ghasemian-Safaei H. Role of gut microbiota in the pathogenesis of colorectal cancer; a review article. Gastroenterol Hepatol Bed Bench. 2018;11(2):101–9.PubMedPubMedCentral Jahani-Sherafat S, Alebouyeh M, Moghim S, Ahmadi Amoli H, Ghasemian-Safaei H. Role of gut microbiota in the pathogenesis of colorectal cancer; a review article. Gastroenterol Hepatol Bed Bench. 2018;11(2):101–9.PubMedPubMedCentral
5.
go back to reference Hale VL, Jeraldo P, Chen J, Mundy M, Yao J, Priya S, Keeney G, Lyke K, Ridlon J, White BA, et al. Distinct microbes, metabolites, and ecologies define the microbiome in deficient and proficient mismatch repair colorectal cancers. Genome medicine. 2018;10(1):78.CrossRefPubMedPubMedCentral Hale VL, Jeraldo P, Chen J, Mundy M, Yao J, Priya S, Keeney G, Lyke K, Ridlon J, White BA, et al. Distinct microbes, metabolites, and ecologies define the microbiome in deficient and proficient mismatch repair colorectal cancers. Genome medicine. 2018;10(1):78.CrossRefPubMedPubMedCentral
6.
go back to reference Purcell RV, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One. 2017;12(2):e0171602.CrossRefPubMedPubMedCentral Purcell RV, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One. 2017;12(2):e0171602.CrossRefPubMedPubMedCentral
7.
go back to reference Bundgaard-Nielsen C, Baandrup UT, Nielsen LP, Sorensen S. The presence of bacteria varies between colorectal adenocarcinomas, precursor lesions and non-malignant tissue. BMC Cancer. 2019;19(1):399.CrossRefPubMedPubMedCentral Bundgaard-Nielsen C, Baandrup UT, Nielsen LP, Sorensen S. The presence of bacteria varies between colorectal adenocarcinomas, precursor lesions and non-malignant tissue. BMC Cancer. 2019;19(1):399.CrossRefPubMedPubMedCentral
8.
go back to reference Toprak NU, Yagci A, Gulluoglu BM, Akin ML, Demirkalem P, Celenk T, Soyletir G. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect. 2006;12(8):782–6.CrossRefPubMed Toprak NU, Yagci A, Gulluoglu BM, Akin ML, Demirkalem P, Celenk T, Soyletir G. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect. 2006;12(8):782–6.CrossRefPubMed
9.
go back to reference Wu S, Morin PJ, Maouyo D, Sears CL. Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology. 2003;124(2):392–400.CrossRefPubMed Wu S, Morin PJ, Maouyo D, Sears CL. Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology. 2003;124(2):392–400.CrossRefPubMed
10.
go back to reference Dahmus JD, Kotler DL, Kastenberg DM, Kistler CA. The gut microbiome and colorectal cancer: a review of bacterial pathogenesis. J Gastrointest Oncol. 2018;9(4):769–77.CrossRefPubMedPubMedCentral Dahmus JD, Kotler DL, Kastenberg DM, Kistler CA. The gut microbiome and colorectal cancer: a review of bacterial pathogenesis. J Gastrointest Oncol. 2018;9(4):769–77.CrossRefPubMedPubMedCentral
11.
go back to reference Viljoen KS, Dakshinamurthy A, Goldberg P, Blackburn JM. Quantitative profiling of colorectal cancer-associated bacteria reveals associations between fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer. PLoS One. 2015;10(3):e0119462.CrossRefPubMedPubMedCentral Viljoen KS, Dakshinamurthy A, Goldberg P, Blackburn JM. Quantitative profiling of colorectal cancer-associated bacteria reveals associations between fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer. PLoS One. 2015;10(3):e0119462.CrossRefPubMedPubMedCentral
12.
go back to reference Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15(9):1016–22.CrossRefPubMedPubMedCentral Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15(9):1016–22.CrossRefPubMedPubMedCentral
14.
go back to reference Boleij A, Hechenbleikner EM, Goodwin AC, Badani R, Stein EM, Lazarev MG, Ellis B, Carroll KC, Albesiano E, Wick EC, et al. The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis. 2015;60(2):208–15.CrossRefPubMed Boleij A, Hechenbleikner EM, Goodwin AC, Badani R, Stein EM, Lazarev MG, Ellis B, Carroll KC, Albesiano E, Wick EC, et al. The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis. 2015;60(2):208–15.CrossRefPubMed
15.
go back to reference Jotwani R, Kato N, Kato H, Watanabe K, Ueno K. Detection of Bacteroides fragilis in clinical specimens by polymerase chain reaction amplification of the neuraminidase gene. Curr Microbiol. 1995;31(4):215–9.CrossRefPubMed Jotwani R, Kato N, Kato H, Watanabe K, Ueno K. Detection of Bacteroides fragilis in clinical specimens by polymerase chain reaction amplification of the neuraminidase gene. Curr Microbiol. 1995;31(4):215–9.CrossRefPubMed
16.
go back to reference Pantosti A, Malpeli M, Wilks M, Menozzi MG, Ambrosio F. Detection of enterotoxigenic Bacteroides fragilis by PCR. J Clin Microbiol. 1997;35(10):2482.PubMedPubMedCentral Pantosti A, Malpeli M, Wilks M, Menozzi MG, Ambrosio F. Detection of enterotoxigenic Bacteroides fragilis by PCR. J Clin Microbiol. 1997;35(10):2482.PubMedPubMedCentral
17.
go back to reference Kato N, Kato H, Watanabe K, Ueno K. Association of Enterotoxigenic Bacteroides fragilis with bacteremia. Clin Infect Dis. 1996;23(Supplement_1):S83–6.CrossRefPubMed Kato N, Kato H, Watanabe K, Ueno K. Association of Enterotoxigenic Bacteroides fragilis with bacteremia. Clin Infect Dis. 1996;23(Supplement_1):S83–6.CrossRefPubMed
18.
go back to reference Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859–904.CrossRefPubMed Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859–904.CrossRefPubMed
19.
go back to reference Rezasoltani S, Asadzadeh Aghdaei H, Dabiri H, Akhavan Sepahi A, Modarressi MH, Nazemalhosseini Mojarad E. The association between fecal microbiota and different types of colorectal polyp as precursors of colorectal cancer. Microb Pathog. 2018;124:244–9.CrossRefPubMed Rezasoltani S, Asadzadeh Aghdaei H, Dabiri H, Akhavan Sepahi A, Modarressi MH, Nazemalhosseini Mojarad E. The association between fecal microbiota and different types of colorectal polyp as precursors of colorectal cancer. Microb Pathog. 2018;124:244–9.CrossRefPubMed
20.
go back to reference Gao Z, Guo B, Gao R, Zhu Q, Qin H. Microbiota disbiosis is associated with colorectal cancer. Front Microbiol. 2015;6:20.PubMedPubMedCentral Gao Z, Guo B, Gao R, Zhu Q, Qin H. Microbiota disbiosis is associated with colorectal cancer. Front Microbiol. 2015;6:20.PubMedPubMedCentral
21.
go back to reference Moore WE, Moore LH. Intestinal floras of populations that have a high risk of colon cancer. Appl Environ Microbiol. 1995;61(9):3202–7.PubMedPubMedCentral Moore WE, Moore LH. Intestinal floras of populations that have a high risk of colon cancer. Appl Environ Microbiol. 1995;61(9):3202–7.PubMedPubMedCentral
22.
go back to reference Ulger Toprak N, Rajendram D, Yagci A, Gharbia S, Shah HN, Gulluoglu BM, Akin LM, Demirkalem P, Celenk T, Soyletir G. The distribution of the bft alleles among enterotoxigenic Bacteroides fragilis strains from stool specimens and extraintestinal sites. Anaerobe. 2006;12(2):71–4.CrossRefPubMed Ulger Toprak N, Rajendram D, Yagci A, Gharbia S, Shah HN, Gulluoglu BM, Akin LM, Demirkalem P, Celenk T, Soyletir G. The distribution of the bft alleles among enterotoxigenic Bacteroides fragilis strains from stool specimens and extraintestinal sites. Anaerobe. 2006;12(2):71–4.CrossRefPubMed
Metadata
Title
The association between fecal enterotoxigenic B. fragilis with colorectal cancer
Authors
Fakhri Haghi
Elshan Goli
Bahman Mirzaei
Habib Zeighami
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-6115-1

Other articles of this Issue 1/2019

BMC Cancer 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine