Project description:Increasing importance in the onset and progression from colonic adenomatous polyps (AP) to colorectal cancer (CRC) has been attributed to the gut microbiota and the oncometabolites they may produce. To comprehensively study the microbial spatial variations and role of microbiota in CRC progression, multiple niches from the gastrointestinal system have to be investigated. We collected saliva, tissue and stool samples from 61 patients, including 46 CRC patients and 15 AP patients, well matched in age and sex, who were undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). For all samples and locations we surveyed microbial composition through 16S ribosomal RNA and metabolites using NMR, and compared them across tissues and disease state, also considering CRC TNM staging. Our result suggest the importance of microbiota communities and derived oncometabolites in CRC development. Such association can be a forerunner for future studies on CRC/AP management.
Project description:Dysbiotic configurations of the human gut microbiota have been linked with colorectal cancer (CRC). Human small non-coding RNAs are also implicated in CRC and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis but their role is less explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens of patients with CRC, or adenomas, and healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We reported a considerable overlap and correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. Furthermore, we identified a combined predictive signature composed by 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC from healthy and adenoma samples (AUC= 0.87). In summary we reported evidence that host-microbiome dysbiosis in CRC can be observed also by altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more accurate tools for diagnostic purposes.