Shifts of Faecal Microbiota During Sporadic Colorectal Carcinogenesis

Giorgia Mori, Simone Rampelli, Beatrice Silvia Orena, Claudia Rengucci, Giulia De Maio, Giulia Barbieri, Alessandro Passardi, Andrea Casadei Gardini, Giovanni Luca Frassineti, Stefano Gaiarsa, Alessandra M Albertini, Guglielmina Nadia Ranzani, Daniele Calistri, Maria Rosalia Pasca, Giorgia Mori, Simone Rampelli, Beatrice Silvia Orena, Claudia Rengucci, Giulia De Maio, Giulia Barbieri, Alessandro Passardi, Andrea Casadei Gardini, Giovanni Luca Frassineti, Stefano Gaiarsa, Alessandra M Albertini, Guglielmina Nadia Ranzani, Daniele Calistri, Maria Rosalia Pasca

Abstract

Gut microbiota has been implicated in the etiopathogenesis of colorectal cancer. The development of colorectal cancer is a multistep process by which healthy epithelium slowly develops into preneoplastic lesions, which in turn progress into malignant carcinomas over time. In particular, sporadic colorectal cancers can arise from adenomas (about 85% of cases) or serrated polyps through the "adenoma-carcinoma" or the "serrated polyp-carcinoma" sequences, respectively. In this study, we performed 16 S rRNA gene sequencing of bacterial DNA extracted from faecal samples to compare the microbiota of healthy subjects and patients with different preneoplastic and neoplastic lesions. We identified putative microbial biomarkers associated with stage-specific progression of colorectal cancer. In particular, bacteria belonging to the Firmicutes and Actinobacteria phyla, as well as members of the Lachnospiraceae family, proved to be specific of the faecal microbiota of patients with preneoplastic lesions, including adenomas and hyperplastic polyps. On the other hand, two families of the Proteobacteria phylum, Alcaligeneaceae and Enterobacteriaceae, with Sutterella and Escherichia/Shigella being the most representative genera, appeared to be associated with malignancy. These findings, once confirmed on larger cohorts of patients, can represent an important step towards the development of more effective diagnostic strategies.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Evaluation of α-diversity in the 5 groups of patients and controls. (A) Chao1 measure of microbial richness; (B) Observed OTUs; (C) Phylogenetic diversity.
Figure 2
Figure 2
Relative abundance of the main bacterial phyla in faecal microbiota of 7 groups of subjects. Histograms based on the proportion of OTUs per average of each group.
Figure 3
Figure 3
Bacterial taxa differentiate 3 clusters: ADK and ADK patients; HP and HRA patients; LRA patients and H subjects. (A) PCoA based on Unweighted UniFrac distances; (B) Superimposition of bacterial genera on the PCoA plot.
Figure 4
Figure 4
Bacterial taxa abundance differentiates ADK from HP, LRA, HRA and ADK-T patients and healthy subjects. (A) PCoA based on Weighted UniFrac distances; (B) Superimposition of microbial genera on the PCoA plot.
Figure 5
Figure 5
Range of microbial diversity in the investigated groups.
Figure 6
Figure 6
Putative faecal biomarkers of sporadic CRC cancerogenesis.

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