Which bacterial toxins are worthy of validation as markers in colorectal cancer screening? A critical review

Mezerova, Kristina; Raclavsky, Vladislav; Starý, L

doi:10.5507/bp.2021.054

Cited by 3 publications

(3 citation statements)

References 111 publications

(147 reference statements)

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“…Given that bacterial genotoxins, including colibactin and Bacteroides fragilis toxin (BFT), play a role in colorectal cancer development, it may be beneficial to utilize as a marker for non-invasive screening of sporadic CRC in combination with a fecal occult blood test (FOBT) [ 203 , 204 ].…”

Section: Employing Microbes or Their Metabolites As A Predictable Mar...mentioning

confidence: 99%

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora

et al. 2022

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In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches’ therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.

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Section: Employing Microbes or Their Metabolites As A Predictable Mar...mentioning

confidence: 99%

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora

et al. 2022

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“…Its biosynthetic mechanism is encoded by the genomic island pks . Colibactin causes DNA double-strand breaks and chromosomal instability in human eukaryotic cells ( Iwasaki et al., 2022 ; Mezerova et al., 2022 ). Cell-lethal distending toxins ( cdts ) induce DNA damage, presumably via DNAse activity, and are closely related enzymes produced by Helicobacter hepaticus that progress to precancerous dysplastic lesions of hepatitis.…”

Section: Introductionmentioning

confidence: 99%

Phenotypicand Genotypic Characterization of Clinical Isolates of Intracellular Adherent–Invasive Escherichia coli Among Different Stages, Family History, and Treated Colorectal Cancer Patients in Iran

Dolatabadi

Fazeli

Karbasizade

et al. 2022

Front. Cell. Infect. Microbiol.

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There is increasing evidence showing that microbial dysbiosis impacts the health and cancer risk of the host. An association between adherent–invasive Escherichia coli (AIEC) and colorectal cancer (CRC) has been revealed. Cyclomodulins (CMs) have been receiving increasing attention for carcinogenic changes. In this study, the incidence and features of intracellular AIEC and cyclomodulin-encoding genes were investigated and the phylogenetic grouping and genetic relatedness were evaluated. E. coli strains were isolated from the colorectal biopsies. Adhesion and invasion assays and intramacrophage cell survival test were performed to separate the AIEC isolates. Virulence genotyping for the genes htrA, dsbA, chuA, and lpfA and the cyclomodulin toxins was also conducted. In addition, phylogenetic grouping of the isolates was determined. Subsequently, repetitive element sequence-based PCR (rep-PCR) fingerprinting was performed. A total of 24 AIEC pathovars were isolated from 150 patients. The prevalence rates of htr, dsbA, and lpfA were 70.83% and that of chuA was 91.66%. The frequencies of the cyclomodulin toxins were as follows: cnf1, 29.2%; cnf2, 25%; colibactin, 29.2%; and cdt, 4.2%; cif was not found. Among the AIEC isolates, 4.2%, 4.2%, 54.2%, 29.2%, and 8.3% with phylotypes A or C, B1, B2, D, and E were identified, respectively. Left-sided colon carcinoma and adenocarcinoma T≥1 stage (CRC2) were colonized by B2 phylogroup AIEC-producing CMs more often than the samples from the other groups. Close genetic relatedness was observed in AIEC isolates with rep-PCR.

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“…Nevertheless, larger studies based on samples from CRC screening populations should be performed to evaluate their potential for risk stratification in CRC screening. Moreover, the challenges associated with using bacterial status in stool at a single point in time as a stratification biomarker for CRC risk may well apply to bacterial toxins in general [42,43].…”

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confidence: 99%

Polyketide synthase positive Escherichia coli one‐time measurement in stool is not informative of colorectal cancer risk in a screening setting

de Klaver,

de Wit,

Bolijn

et al. 2024

The Journal of Pathology

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Environmental factors like the pathogenicity island polyketide synthase positive (pks+) Escherichia coli (E. coli) could have potential for risk stratification in colorectal cancer (CRC) screening. The association between pks+ E. coli measured in fecal immunochemical test (FIT) samples and the detection of advanced neoplasia (AN) at colonoscopy was investigated. Biobanked FIT samples were analyzed for both presence of E. coli and pks+ E. coli and correlated with colonoscopy findings; 5020 CRC screening participants were included. Controls were participants in which no relevant lesion was detected because of FIT‐negative results (cut‐off ≥15 μg Hb/g feces), a negative colonoscopy, or a colonoscopy during which only a nonadvanced polyp was detected. Cases were participants with AN [CRC, advanced adenoma (AA), or advanced serrated polyp (ASP)]. Existing DNA isolation and quantitative polymerase chain reaction (qPCR) procedures were used for the detection of E. coli and pks+ E. coli in stool. A total of 4542 (90.2%) individuals were E. coli positive, and 1322 (26.2%) were pks+ E. coli positive. The prevalence of E. coli in FIT samples from individuals with AN was 92.9% compared to 89.7% in FIT samples of controls (p = 0.010). The prevalence of pks+ E. coli in FIT samples from individuals with AN (28.6%) and controls (25.9%) was not significantly different (p = 0.13). The prevalences of pks+ E. coli in FIT samples from individuals with CRC, AA, or ASP were 29.6%, 28.3%, and 32.1%, respectively. In conclusion, the prevalence of pks+ E. coli in a screening population was 26.2% and did not differ significantly between individuals with AN and controls. These findings disqualify the straightforward option of using a snapshot measurement of pks+ E. coli in FIT samples as a stratification biomarker for CRC risk. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Which bacterial toxins are worthy of validation as markers in colorectal cancer screening? A critical review

Cited by 3 publications

References 111 publications

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora

Phenotypicand Genotypic Characterization of Clinical Isolates of Intracellular Adherent–Invasive Escherichia coli Among Different Stages, Family History, and Treated Colorectal Cancer Patients in Iran

Polyketide synthase positive Escherichia coli one‐time measurement in stool is not informative of colorectal cancer risk in a screening setting

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