Abstract
Colorectal cancer (CRC) development is a gradual process in which progressive histological alterations of the intestinal mucosa damage occur over years. This process can be influenced by modifiable external factors such as lifestyle and diet. Most CRC cases (>80%) originate from conventional adenomas through the adenomatous pathway and usually harbour dysplastic cells, whereas the serrated pathway is less frequent (<20% cases) and comprises hyperplastic polyps and other polyps containing dysplastic cells. The aim of the present work was to shed light on alterations of the faecal metabolome associated with hyperplastic polyps and conventional adenomas. Metabolites were analysed by Reversed-Phase High-Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry (RP/HPLC-Q/TOF-MS/MS) and Hydrophilic Interaction Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry (HILIC-Q/TOF-MS/MS) and the results were integrated. Comparisons were performed between controls without mucosal lesions and the polyps' group, hyperplastic polyps versus conventional adenomas, and hyperplastic polyps or conventional adenomas versus controls. Alterations of metabolites in specific biochemical modules differentiated hyperplastic polyps and conventional adenomas. The metabolome of the hyperplastic polyps was characterized by an enrichment in glycerophospholipids and an altered metabolism of the degradation pathways of xanthines/purines and pyrimidines, whereas the enrichment in some phenolic compounds and disaccharides, all of them from exogenous origin, was the main differential faecal signature of conventional adenomas. Further research could help to elucidate the contribution of diet and the intestinal microbiota to these metabolomics alterations.