MeaTIc

The aim of Meatic project is to understand the role of the gut microbiome as determinant of the effect of diet on colorectal cancer risk and to identify specific associated microbiome profiles. We compared in humans (WP1) and experimental animals (WP2-WP3-WP4), a high-risk meat-based diet (MBD) with a pesco-vegetarian diet (PVD) associated with a lower CRC risk and a MBD diet medium risk supplemented with α-tocopherol (MBD-T). In human study (WP1), cholesterol, triglyceride, and ferritin blood levels were significantly different comparing the three different diets. Considering the primary outcome, our results indicate that the MBD was associated with an increase in markers of colon cancer risk as faecal waters (FW) genotoxicity. Instead, a complete protection from the effect of the MBD was found upon supplementation of the meat-based diet with alpha-tocopherol. Regarding the microbial metabolome, we found significantly differences in the 3 diets by identifying specific metabolic biomarkers for the PVD diet compared to the meat-based diets, resulting more discriminating than those of the metataxonomic profiles.

For AOM induced rat carcinogenesis (WP2), urinary and faecal lipid peroxidation biomarkers indicate an increase in luminal lipid peroxidation in the colon of rats fed meat-based diets when compared to the Ctrl or the PVD, with no significant effect of α-tocopherol supplementation. In addition, gut permeability was decreased by the PVD, with no effect of MBD and MBD-T. The analysis on microbiota composition indicated that dietary intervention significantly modified bacterial communities generating clearly distinguishable profiles, especially for the PVD.  The metabolomics analysis identified a set of seven metabolites able to classify different diet groups and expanding those we found another set of 50 highly correlated.

For the Pirc rats (WP3), our results showed a significantly lower number of colon and total tumours in the rats treated with the PVD, while MBD and MBD-T presented similar numbers. Apoptosis in the normal mucosa was significantly higher in the PVD compared with the two groups fed with meat. Metataxonomic analysis indicated a significant difference of the bacterial community between the 3 diets, in particular of the PVD with respect to all others. In particular, we found Prevotellaceae, Lachnospiraceae, Ruminococcaceae abundance in PVD group, showing the strongest inverse relation to colon tumours. Metabolomics analyses identifies specific metabolomics profiles characteristic of the three diets. 

The faecal microbiota transplant (WP4) from Pirc rats fed the three different diets into germ–free rats in which colon carcinogenesis was induced with AOM, demonstrated that faecal microbiota with relative metabolites was able to transmit cancer risk: WT rats transplanted with the meat-based diet faeces, had a significantly higher number of preneoplastic lesions related with specific microbiome profile and relative metabolites.