Introduction The human intestinal tract is a complex microbial ecosystem unique to every individual and contributing sufficient metabolic equivalents to be considered an organ in its own right. Dysbiosis is thought to contribute to the chronic inflammation which is involved in colorectal cancer (CRC) development. We have shown that the premalignant adenoma stage of CRC is underpinned by chronic inflammation and hypothesise that the colonic microbiota is an important driver of neoplastic progression. The aim of the study was to compare bacterial diversity in adenomas and paired adjacent normal colonic tissue.
Methods 72 patients undergoing colonoscopy as part of the national bowel cancer screening programme were recruited. All patients underwent polypectomy for large adenomas (> 1cm). Denaturing gradient gel electrophoresis (DGGE on all subjects) and pyrosequencing (18 subjects) were used to compare the bacterial diversity present between the adenoma and adjacent normal paired tissue samples.
Results 46% of patients showed differences in microbial diversity by DGGE analysis between adenoma and adjacent normal tissue. 21% had only limited differences whilst 79% showed dramatically altered diversity profiles. Phylum-level comparisons across the study cohort, based on sequencing, revealed no statistically significant differences for the Bacteroidetes, Firmicutes and Proteobacteria phyla. When samples were split based on DGGE analysis (i.e. similar or different DGGE profiles between paired polyp and normal mucosa), eight of the possible 10 phyla showed statistically significant differences. Collectively samples with similar profiles between polyp and normal tissue (DGGE ‘same’ group) had higher levels of Bacteroidetes and lower numbers of Actinobacteria, Firmicutes and Proteobacteria than the DGGE ‘different’ group. However when genus-level comparisons were assessed the DGGE ‘different’ sample pairs demonstrated a much greater level of dysbiosis. The levels of normal commensal genera were reduced and there was evidence of large numbers of potentially pathogenic bacteria including Shigella, Enterobacter and Fusobacteria spp.
Conclusion Differences in microbial diversity harboured by a significant number of polyps compared to their immediately adjacent normal mucosa point to an important role for these bacteria in CRC progression. We hypothesise that the disturbed microbial homeostasis in these polyps, in genetically predisposed individuals and taking into account multiple environmental factors, underpins the pathogenesis of colorectal neoplasia. The identification of a “harmful” pro-inflammatory microbiota that is associated with precancerous stages (i.e. adenomas) offers the potential for manipulations of this microbiota with probiotic, prebiotic and indeed antibiotic means.
Disclosure of Interest None Declared.
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