The impact of fecal microbiome on diet-related colorectal cancer risk: contrasting red meat-based and pesco-vegetarian diets in rodent model.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths globally. The geographical distribution of its incidence highlights the significant role played by environmental factors and dietary habits in its development. This study centers on investigating the role of the intestinal microbiome profile and its associated metabolites in CRC risk, with the aim of determining whether reduced consumption of red/processed meat can lead to a decrease in potentially toxic and/or carcinogenic metabolites. In two animal models of colon carcinogenesis (chemically induced by azoxymethane and genetically driven by mutations in the Apc gene - Pirc rats), we compared a high-risk meat-based diet (MBD) with a low-risk pesco-vegetarian diet (PVD). An additional group followed an MBD diet supplemented with tocopherol (MBD-T), which could potentially mitigate the risk associated with red/processed meat consumption. Across all animal models, we observed a diverse microbial community among the three diets, with certain bacterial genera showing a strong inverse correlation with both tumors and neoplastic lesions. Through fecal microbiota transplantation from Pirc rats to germ-free recipient rats with azoxymethaneinduced carcinogenesis, we demonstrated that the fecal microbiome with specific metabolomic profiles was capable of transmitting cancer risk. Rats receiving MBD fecal transplants exhibited a significantly higher number of preneoplastic lesions associated with specific microbial and metabolomic profiles. Our findings illustrate how diet can directly modulate the composition of the intestinal microbiome and, in turn, influence the risk of colorectal cancer in various animal models of carcinogenesis.