Colonization of the gut mucosa of colorectal cancer patients by pathogenic mucosa-associated Escherichia coli strains

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second most deadly cancer in the world [1]. CRC is a complex disease with multiple risk factors. The most important risk factors for this type of cancer are race and ethnicity, age, hereditary mutations, inflammatory bowel disease (IBD), obesity, smoking, alcohol consumption and diabetes[2].

Recently literature suggests that intestinal microbiota could be associated with colorectal carcinogenesis [3], [4], [5], [6]. The human gut microbiota contains a collection of various microbes such as bacteria, fungi, viruses and archaea that live in the normal intestinal tract [7,8]. Gut microbiota performs a vital role in bodily functions including metabolization of dietary compounds, maintaining the physiological functions of the intestinal tract and modulating the host immunity [7]. Various factors such as environment trigger, genetic defect and diet can change the composition of the gut microbiota, the so called microbial dysbiosis [9]. Microbiota dysbiosis has been recognized as a cause of various disorders like obesity, diabetes, allergies, CRC and IBD [10]. Levels of some bacteria such as Prevotella, Bacteroides spp. [11], Escherichia coli, Bacteroides fragilis and Streptococcus gallolyticus have been found to be higher in CRC biopsy specimens than in healthy tissues [12].

Given that E. coli is the most common human gut commensal facultative anaerobic resident [13], a significant number of studies have clearly shown that there is a clear link between specific strains of this bacterium and CRC [14], [15], [16]. Mucosa-associated E. coli especially cyclomodulin-positive strains are colonized more frequently in gut mucosa of patients with CRC in comparison to the normal mucosa [16]. Mucosa-associated E.coli has an important role in the pathogenesis of CRC by stimulation of a pro-inflammatory response [17] and production of toxins [18]. It has also been observed that such E.coli strains from CRC patients carry specific virulence factors of the extra-intestinal pathogenic E. coli (ExPEC), especially uropathogenic E. coli (UPEC) such as pyelonephritis-associated pilus (P fimbriae or pap) Yersinia bactin receptor (fyuA), the heme receptor (chuA) and vacuolating autotransporter toxin (vat) [19]. More noteworthy, enteropathogenic Escherichia coli (EPEC) strains have been found more frequently in the tissue samples of CRC patients than those with healthy samples, so there may be a correlation between some strains of diarrheagenic E. coli (DEC) and CRC [20].

To our knowledge, little data are available on the general characteristics of the mucosa-associated E. coli strains from CRC patients. Therefore, this study was aimed to evaluate the genetic diversity, pathotypes and virulence gene profile of mucosa-associated E. coli from patients with CRC and healthy subjects.

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