A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer

Toprak, N. Ulger; Yağcı, Ayşegül; Güllüoğlu, Bahadır M.; Akın, Mehmet; Demirkalem, Pakize; Celenk, Tuncay; Sõyletır, Gũner

doi:10.1111/j.1469-0691.2006.01494.x

Cited by 365 publications

(164 citation statements)

References 21 publications

(30 reference statements)

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“…Subsequent mechanistic studies identified that Stat3 activation with induction of mucosal IL-17 responses were involved [24]. Confirmation of involvement in human CRC is currently limited, although a study looking at ETBF prevalence in a CRC population detected ETBF more often CRC cases compared to matched controls [25]. …”

Section: Specific Microbes and Crc Riskmentioning

confidence: 99%

Gastrointestinal Microbiota and Colon Cancer

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2016

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The human gut microbiota plays a major role in the development and maintenance of good health. Many recent studies have attempted to define links between microbiota residents, their function and the development of colorectal cancer (CRC). Gut microbiota drive the development of inflammation within the colon and such inflammation is implicated in colonic neoplastic development. Although the precise mechanisms through which the microbiota is involved in cancer development remain elusive, the message is clear: the microbiota contributes to cancer risk by influencing a number of key host processes. It is also recognized that we have the ability to influence the role of the gut microbiota by considering our nutritional intake. We have always known that ‘we are what we eat' but it is also true that ‘they (our gut microbiota) are what we eat'. We therefore have a huge opportunity to positively influence our health through microbial manipulation. There is now a clear need to move past defining the constituents of the gastrointestinal microbiota and to focus more on understanding the functional capabilities of the resident microbial community and how this impacts on host health. One such emerging concept is the development of microbial biofilms which can form in the gut in conjunction with CRC tissue. By better understanding of the interaction between the host and its resident microbiota, in the context of health and cancer development, we will open new therapeutic and diagnostic opportunities for reducing the CRC global health burden.

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Section: Specific Microbes and Crc Riskmentioning

confidence: 99%

Gastrointestinal Microbiota and Colon Cancer

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2016

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“…However, we note that the primers used by Toprak and colleagues (2) are also designed against the Moncrief sequence and, accordingly, are markedly different from the published bft sequences (Table 1). This study reports a high carriage rate for ETBF among CRC patients, and with no reference to sequencing of PCR products, the possibility that these primers are associated with a high rate of false positives cannot be excluded.…”

Section: Toprak Et Al (2) Gagccgaagacggtgtatgtgatttgt Tgctcagcgcccagmentioning

confidence: 79%

“…olonic carriage of enterotoxigenic Bacteroides fragilis (ETBF) is reportedly more common in people presenting with colorectal cancer (CRC) than in healthy controls (1)(2)(3), fueling speculation that persistent carriage of these bacteria may "drive" colon carcinogenesis (4). Our aim was to use a bft amplification protocol to determine the prevalence of toxin-producing strains of B. fragilis in CRC patient stool samples.…”

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PCR Detection of the Bacteroides fragilis Enterotoxin Gene Relies on Robust Primer Design

2016

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Colonic carriage of enterotoxigenic Bacteroides fragilis (ETBF) is reportedly more common in people presenting with colorectal cancer (CRC) than in healthy controls (1-3), fueling speculation that persistent carriage of these bacteria may "drive" colon carcinogenesis (4). Our aim was to use a bft amplification protocol to determine the prevalence of toxin-producing strains of B. fragilis in CRC patient stool samples.Sixty-one patients histologically diagnosed with CRC consented to provide a stool sample prior to surgery. The study was approved by the Upper South A Regional Ethics Committee. Each stool was cultured anaerobically on Bacteroides bile esculin (BBE) agar (Fort Richard Laboratories, Auckland, New Zealand). After 48 h of incubation at 37°C, all colonies were swept off the plates into 500 l of sterile water and heated for 10 min at 99°C.Each sample was screened for evidence of the bft gene using Pantosti (5) and Odamaki (6) primer sets. The PCR mixtures for the Pantosti toxin primers consisted of a 10-l volume containing 5 pmol of each primer, 200 nM deoxynucleoside triphosphates (dNTPs), 2 mM MgCl 2 , 1ϫ enzyme buffer, 0.5 U HotFire polymerase (Solis Biodyne, Tartu, Estonia), and 0.5 l DNA template. The PCR mixture for amplification of the toxin gene by Odamaki primers differed by using 1.5 mM MgCl 2 and by the addition of 1 l of S solution (Solis Biodyne, Tartu, Estonia). Amplification consisted of a 15-min incubation at 95°C followed by 35 cycles of 30 s of denaturation at 95°C, 30 s of annealing (52°C and 66°C, respectively), and 30 s of extension at 72°C, followed by a final extension step of 2 min at 72°C. Positive and no-template controls were included in each experiment. Products were run on a 1.5% agarose gel, and fragments were visualized using SYBRSafe dye (Invitrogen, Carlsbad, CA, USA).Results showed that the Pantosti primers amplified only 5 ETBF samples while the Odamaki primers amplified 10. Only four samples amplified by Odamaki primers were recognized by the Pantosti primers, while one sample amplified by the Pantosti primers was not recognized by the Odamaki primers (Table 1). ETBF-positive samples were further analyzed by subtype-specific PCR (6). Notably, the Pantosti primers gave no discernible product other than BFT-1, whereas samples that yielded positive bft fragments with Odamaki primers only were identified as containing BFT-2 and -3 subtypes. This finding was confirmed using both primer sets to amplify DNA extracted from three ETBF reference strains (strains VPI 13784and Korea 570 [9], generously supplied by Cynthia Sears). The Odamaki primer set amplified all three subtypes well, whereas the Pantosti primers amplified less efficiently from BFT-2 and very poorly from BFT-3 (Fig. 1). Collectively, these results suggest that Pantosti primers may miss some BFT-2-and BFT-3-containing samples.The Pantosti primer set, still in common use (3, 10), was designed against the sequence published by Moncrief and col-

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“…B. fragilis toxin specifically cleaves the extracellular domain of the zonula adherens protein E-cadherin, which is the principal structural component of the zonula adherens and is responsible for cell-to-cell adhesion. Fragilysin, which causes cleavage of the extracellular domain of E-cadherin, leads to complete degradation of this protein [25]. …”

Section: Gut Microbiota and Crcmentioning

confidence: 99%

“…Activation of β-catenin signaling via mutations in one or more of the APC complex proteins contributes to the development of inherited and sporadic forms of CRC and possibly other cancers. Toprak et al [25], by investigating the prevalence of ETBF in stool specimens from 73 CRC patients and 59 controls, found the enterotoxin gene in 38% of the isolates from CRC patients compared with 12% of the isolates from the control group. More recently, Wu et al [27] showed that ETBF triggers colitis and strongly induces CRC in multiple intestinal neoplasia mice.…”

Section: Gut Microbiota and Crcmentioning

confidence: 99%

Contribution of Gut Microbiota to Colonic and Extracolonic Cancer Development

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2011

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It is estimated that 20% of malignancies worldwide can be attributed to infections, i.e. about 1.2 million cases per year. A typical example of the association between bacterial infection and gastrointestinal malignancies is Helicobacter pylori infection with both gastric cancer and mucosa-associated lymphoid tissue lymphoma. Bacteria are an important component of the human body. The human intestine contains >500 different types of microorganisms, the ‘gut microbiota’, that play important functions such as energetic metabolism, proliferation and survival of epithelial cells, and protection against pathogens. Chronic alteration of intestinal microbiota homeostasis, ‘dysbiosis’, could promote many diseases, including cancer. The mechanisms by which bacteria may induce carcinogenesis include chronic inflammation, immune evasion, and immune suppression. There are three effector pathways of T helper (Th) cell differentiation: Th1 responses promoted by procarcinogenic signal transducer and activator of transcription (Stat)1 and Stat4 signaling, Th2 responses promoted by Stat6 signaling, and Th17 responses promoted by Stat3 signaling. Interestingly, Th1 responses, driven by IL-12 and characterized by IFN-γ production, are typically anticarcinogenic, whereas Th17 responses are activated in various cancers. Furthermore, a T regulatory response, driven by IL-10 and TGF-β, counterbalances the proinflammatory effect of Th17 responses. Elevated numbers of T regulatory cells suppress the innate and adaptive immune responses, thereby contributing to tumor progression. The emerging relationship between gut microbiota and cancer has prompted new ways of thinking about cancer prevention and has led to the development of noninvasive diagnostic tests and innovative treatments, such as with probiotics. However, although in vitro and animal model studies suggest a protective anticancer effect of probiotics, the results of human epidemiological studies are controversial.

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A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer

Cited by 365 publications

References 21 publications

Gastrointestinal Microbiota and Colon Cancer

Gastrointestinal Microbiota and Colon Cancer

PCR Detection of the Bacteroides fragilis Enterotoxin Gene Relies on Robust Primer Design

Contribution of Gut Microbiota to Colonic and Extracolonic Cancer Development

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