Abstract

The composition of the human intestinal microbiota is linked to health status. The aim was to analyze the microbiota of normal and colon cancer patients in order to establish cancer-related dysbiosis.Patients and MethodsStool bacterial DNA was extracted prior to colonoscopy from 179 patients: 60 with colorectal cancer, and 119 with normal colonoscopy. Bacterial genes obtained by pyrosequencing of 12 stool samples (6 Normal and 6 Cancer) were subjected to a validated Principal Component Analysis (PCA) test. The dominant and subdominant bacterial population (C. leptum, C. coccoides, Bacteroides/Prevotella, Lactobacillus/Leuconostoc/Pediococcus groups, Bifidobacterium genus, and E. coli, and Faecalibacterium prausnitzii species) were quantified in all individuals using qPCR and specific IL17 producer cells in the intestinal mucosa were characterized using immunohistochemistry.FindingsPyrosequencing (Minimal sequence 200 nucleotide reads) revealed 80% of all sequences could be assigned to a total of 819 taxa based on default parameter of Classifier software. The phylogenetic core in Cancer individuals was different from that in Normal individuals according to the PCA analysis, with trends towards differences in the dominant and subdominant families of bacteria. Consequently, All-bacteria [log10 (bacteria/g of stool)] in Normal, and Cancer individuals were similar [11.88±0.35, and 11.80±0.56, respectively, (P = 0.16)], according to qPCR values whereas among all dominant and subdominant species only those of Bacteroides/Prevotella were higher (All bacteria-specific bacterium; P = 0.009) in Cancer (-1.04±0.55) than in Normal (-1.40±0.83) individuals. IL17 immunoreactive cells were significantly expressed more in the normal mucosa of cancer patients than in those with normal colonoscopy.ConclusionThis is the first large series to demonstrate a composition change in the microbiota of colon cancer patients with possible impact on mucosal immune response. These data open new filed for mass screening and pathophysiology investigations.

Highlights

  • The human colon contains up to 1014 bacteria [1]

  • Since this study was carried out, the human colonic microbiota has emerged as a major environmental factor that appears to modulate the risk of colonic cancer, and dysbiosis in the gut microbiota is believed to be a factor underlying the development of disease in genetically-predisposed individuals

  • We identified 18 bacterial genera with an abundance of more than 1%, and these genera included 75% of the sequences

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Summary

Introduction

The human colon contains up to 1014 bacteria [1] They play a major role in the fermentation of residual food, the modulation of gut immune function, and protection against pathogens and diseases [2,3,4,5]. Moore and co-workers reported that 13 bacterial species were significantly associated with a high risk of colon cancer and the Western diet [1]. Their results were somewhat unconvincing because they investigated a small number of subjects and no intestinal investigation i.e. radiology or colonoscopy was performed. There is no evidence whether dysbiosis does occur in colon cancer

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