Prevalence of pks + bacteria and enterotoxigenic Bacteroides fragilis in patients with colorectal cancer

Gut Pathogens - Tập 14 Số 1
Manon Oliero1, Roy Hajjar1, Thibault Cuisiniere1, Gabriela Fragoso1, Annie Calvé1, François Dagbert2, Rasmy Loungnarath2, Herawaty Sebajang2, Frank Schwenter2, Ramsès Wassef2, Richard Ratelle2, Éric De Broux2, Carole Richard2, Manuela M. Santos3
1Nutrition and Microbiome Laboratory, Institut du cancer de Montréal, Centre de recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), 900 Rue Saint Denis, Montréal, QC, H2X 0A9, Canada
2Digestive Surgery Service, Department of Surgery, Centre hospitalier de l’Université de Montréal (CHUM), 1000 Rue Saint-Denis, Montréal, Québec, H2X 0C1, Canada
3Department of Medicine, Faculty of Medicine, Université de Montréal, 2900 Boulevard Édouard-Montpetit, Montréal, QC, H3T 1J4, Canada

Tóm tắt

Abstract Background

Colorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer deaths worldwide. CRC patients present with an increase in pathogens in their gut microbiota, such as polyketide synthase-positive bacteria (pks +) and enterotoxigenic Bacteroides fragilis (ETBF). The pks + Escherichia coli promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). ETBF is a procarcinogenic bacterium producing the B. fragilis toxin (bft) that promotes colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes.

Methods

Fecal samples were collected from healthy controls (N = 62) and CRC patients (N = 94) from the province of Québec (Canada), and a bacterial DNA extraction was performed. Fecal DNA samples were then examined for the presence of the pks island gene and bft using conventional qualitative PCR.

Results

We found that a high proportion of healthy controls are colonized by pks + bacteria (42%) and that these levels were similar in CRC patients (46%). bft was detected in 21% of healthy controls and 32% of CRC patients, while double colonization by both pks + bacteria and ETBF occurred in 8% of the healthy controls and 13% of the CRC patients. Most importantly, we found that early-onset CRC (< 50 years) patients were significantly less colonized with pks + bacteria (20%) compared to late-onset CRC patients (52%).

Conclusions

Healthy controls had similar levels of pks + bacteria and ETBF colonization as CRC patients, and their elevated levels may place both groups at greater risk of developing CRC. Colonization with pks + bacteria was less prevalent in early-compared to late-onset CRC.

Từ khóa


Tài liệu tham khảo

Song M, Chan AT, Sun J. Influence of the gut microbiome, diet, and environment on risk of colorectal cancer. Gastroenterology. 2020;158(2):322–40.

Wirbel J, Pyl PT, Kartal E, Zych K, Kashani A, Milanese A, et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019;25(4):679–89. https://doi.org/10.1038/s41591-019-0406-6.

Kaper JB, Nataro JP, Mobley HLT. Pathogenic Escherichia coli. Nat Rev Microbiol. 2004;2(2):123–40. https://doi.org/10.1038/nrmicro818.

Homburg S, Oswald E, Hacker J, Dobrindt U. Expression analysis of the colibactin gene cluster coding for a novel polyketide in Escherichia coli. FEMS Microbiol Lett. 2007;275(2):255–62.

Xue M, Kim CS, Healy AR, Wernke KM, Wang Z, Frischling MC, et al. Structure elucidation of colibactin and its DNA cross-links. Science. 2019;365(6457):eaax2685.

Secher T, Samba-Louaka A, Oswald E, Nougayrède J-P. Escherichia coli producing colibactin triggers premature and transmissible senescence in mammalian cells. PLOS ONE. 2013;8(10):e77157. https://doi.org/10.1371/journal.pone.0077157.

Arthur JC, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis JM, Fan TJ, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 2012;338(6103):120–3.

Dejea CM, Fathi P, Craig JM, Boleij A, Taddese R, Geis AL, et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science. 2018;359(6375):592–7.

Lopès A, Billard E, Casse AH, Villéger R, Veziant J, Roche G, et al. Colibactin-positive Escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer. Int J Cancer. 2020;146(11):3147–59. https://doi.org/10.1002/ijc.32920.

Putze J, Hennequin C, Nougayrede JP, Zhang W, Homburg S, Karch H, et al. Genetic structure and distribution of the colibactin genomic island among members of the family Enterobacteriaceae. Infect Immun. 2009;77(11):4696–703.

Strakova N, Korena K, Karpiskova R. Klebsiella pneumoniae producing bacterial toxin colibactin as a risk of colorectal cancer development—a systematic review. Toxicon. 2021;197:126–35.

Tsunematsu Y, Hosomi K, Kunisawa J, Sato M, Shibuya N, Saito E, et al. Mother-to-infant transmission of the carcinogenic colibactin-producing bacteria. BMC Microbiol. 2021;21(1):235.

Tenaillon O, Skurnik D, Picard B, Denamur E. The population genetics of commensal Escherichia coli. Nat Rev Microbiol. 2010;8(3):207–17. https://doi.org/10.1038/nrmicro2298.

Stoppe NC, Silva JS, Carlos C, Sato MIZ, Saraiva AM, Ottoboni LMM, et al. Worldwide phylogenetic group patterns of Escherichia coli from commensal human and wastewater treatment plant isolates. Front Microbiol. 2017;8:2512. https://doi.org/10.3389/fmicb.2017.02512.

Sears CL. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin Microbiol Rev. 2009;22(2):349–69.

Ulger Toprak N, Yagci A, Gulluoglu BM, Akin ML, Demirkalem P, Celenk T, et al. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect. 2006;12(8):782–6.

Kim JM, Lee JY, Kim Y-J. Inhibition of apoptosis in Bacteroides fragilis enterotoxin-stimulated intestinal epithelial cells through the induction of c-IAP-2. Eur J Immunol. 2008;38(8):2190–9. https://doi.org/10.1002/eji.200838191.

Wu S, Morin PJ, Maouyo D, Sears CL. Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology. 2003;124(2):392–400.

Hwang S, Lee CG, Jo M, Park CO, Gwon S-Y, Hwang S, et al. Enterotoxigenic Bacteroides fragilis infection exacerbates tumorigenesis in AOM/DSS mouse model. Int J Med Sci. 2020;17(2):145–52.

Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, 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.

INRA. IHMS. 2015. http://www.human-microbiome.org/. Accessed 12 may 2021.

Gao W, Zhang W, Meldrum DR. RT-qPCR based quantitative analysis of gene expression in single bacterial cells. J Microbiol Methods. 2011;85(3):221–7.

Liu C, Song Y, McTeague M, Vu AW, Wexler H, Finegold SM. Rapid identification of the species of the Bacteroides fragilis group by multiplex PCR assays using group- and species-specific primers. FEMS Microbiol Lett. 2003;222(1):9–16.

Eklof V, Lofgren-Burstrom A, Zingmark C, Edin S, Larsson P, Karling P, et al. Cancer-associated fecal microbial markers in colorectal cancer detection. Int J Cancer. 2017;141(12):2528–36.

Shimpoh T, Hirata Y, Ihara S, Suzuki N, Kinoshita H, Hayakawa Y, et al. Prevalence of pks-positive Escherichia coli in Japanese patients with or without colorectal cancer. Gut Pathog. 2017;9:35.

Nouri R, Hasani A, Masnadi Shirazi K, Alivand MR, Sepehri B, Sotoudeh S, et al. Mucosa-associated <i>Escherichia coli</i> in colorectal cancer patients and control subjects: variations in the prevalence and attributing features. Can J Infect Dis Med Microbiol. 2021;2021:2131787. https://doi.org/10.1155/2021/2131787.

Iyadorai T, Mariappan V, Vellasamy KM, Wanyiri JW, Roslani AC, Lee GK, et al. Prevalence and association of pks+ Escherichia coli with colorectal cancer in patients at the University Malaya Medical Centre, Malaysia. PLoS ONE. 2020;15(1):e0228217.

Vernia F, Longo S, Stefanelli G, Viscido A, Latella G. Dietary factors modulating colorectal carcinogenesis. Nutrients. 2021;13(1):143.

Arima K, Zhong R, Ugai T, Zhao M, Haruki K, Akimoto N, et al. Western-style diet, pks Island-carrying Escherichia coli, and colorectal cancer: analyses from two large prospective cohort studies. Gastroenterology. 2022;163(4):862–74.

Lee-Six H, Olafsson S, Ellis P, Osborne RJ, Sanders MA, Moore L, et al. The landscape of somatic mutation in normal colorectal epithelial cells. Nature. 2019;574(7779):532–7. https://doi.org/10.1038/s41586-019-1672-7.

O’Sullivan DE, Sutherland RL, Town S, Chow K, Fan J, Forbes N, et al. Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis. Clinical Gastroenterology and Hepatology. 2022;20(6):1229-40.e5. https://www.sciencedirect.com/science/article/pii/S1542356521000872

Puzzono M, Mannucci A, Grannò S, Zuppardo RA, Galli A, Danese S, et al. The role of diet and lifestyle in early-onset colorectal cancer: a systematic review. Cancers (Basel). 2021;13(23):5933.

Hur J, Otegbeye E, Joh H-K, Nimptsch K, Ng K, Ogino S, et al. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut. 2021;70(12):2330.

Sinicrope FA. Increasing incidence of early-onset colorectal cancer. N Engl J Med. 2022;386(16):1547–58. https://doi.org/10.1056/NEJMra2200869.

Yang Y, Du L, Shi D, Kong C, Liu J, Liu G, et al. Dysbiosis of human gut microbiome in young-onset colorectal cancer. Nat Commun. 2021;12(1):6757. https://doi.org/10.1038/s41467-021-27112-y.

Matsumiya Y, Suenaga M, Ishikawa T, Hanaoka M, Iwata N, Masuda T, et al. Clinical significance of Bacteroides fragilis as potential prognostic factor in colorectal cancer patients. J Clin Oncol. 2022;40:137. https://doi.org/10.1200/JCO.2022.40.4_suppl.137.

Haghi F, Goli E, Mirzaei B, Zeighami H. The association between fecal enterotoxigenic B. fragilis with colorectal cancer. BMC cancer. 2019;19(1):879.

Zamani S, Taslimi R, Sarabi A, Jasemi S, Sechi LA, Feizabadi MM. Enterotoxigenic Bacteroides fragilis: a possible etiological candidate for bacterially-induced colorectal precancerous and cancerous lesions. Front Cell Infect Microbiol. 2020;9:449.

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.