Gut microbiota drives colon cancer risk associated with diet: a comparative analysis of meat-based and pesco-vegetarian diets
Abstract
Colorectal cancer (CRC) risk is strongly affected by dietary habits with red and processed meat increasing risk, and foods rich in dietary fibres considered protective. Dietary habits also shape gut microbiota, but the role of the combination between diet, the gut microbiota, and the metabolite profile on CRC risk is still missing an unequivocal characterisation.
Methods
To investigate how gut microbiota affects diet-associated CRC risk, we fed Apc-mutated PIRC rats and azoxymethane (AOM)-induced rats the following diets: a high-risk red/processed meat-based diet (MBD), a normalised risk diet (MBD with α-tocopherol, MBDT), a low-risk pesco-vegetarian diet (PVD), and control diet. We then conducted faecal microbiota transplantation (FMT) from PIRC rats to germ-free rats treated with AOM and fed a standard diet for 3 months. We analysed multiple tumour markers and assessed the vaiations in the faecal microbiota using 16S rRNA gene sequencing together with targeted-and untargeted-metabolomics analyses.
Results
In both animal models, the PVD group exhibited significantly lower colon tumorigenesis than the MBD ones, consistent with various CRC biomarkers. Faecal microbiota and its metabolites also revealed significant dietdependent profiles. Intriguingly, when faeces from PIRC rats fed these diets were transplanted into germ-free rats, those transplanted with MBD faeces developed a higher number of preneoplastic lesions together with distinctive diet-related bacterial and metabolic profiles. PVD determines a selection of nine taxonomic markers mainly belonging to Lachnospiraceae and Prevotellaceae families exclusively associated with at least two different animal models, and within these, four taxonomic markers were shared across all the three animal models. An inverse correlation between nonconjugated bile acids and bacterial genera mainly belonging to the Lachnospiraceae and Prevotellaceae families (representative of the PVD group) was present, suggesting a potential mechanism of action for the protective effect of these genera against CRC.
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