Combination of a pesco-vegetarian diet with non-steroidal anti-inflammatory drugs for colorectal cancer prevention: tumor suppression and gut microbiota modulation in Apc- mutated PIRC rats

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with genetic predispositions such as FAP contributing significantly to early-onset disease. This study investigated the chemopreventive potential of two non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA) and sulindac (SU), in combination with a pesco-vegetarian diet (PVD), using Apc -mutated PIRC rats, a well-established model of CRC. Animals were treated over three months with two doses of ASA or a single dose of SU, and tumor burden and gut microbiota composition were assessed. Results confirmed the robust protective effect of the PVD diet in reducing the intestinal tumorigenesis, particularly in the colon, independent of pharmacological treatment. ASA treatment, especially at the higher dose, significantly reduced tumour incidence in both dietary groups, with additive effects seen in combination with PVD, while SU did not show a significant protective effect. Microbiota analysis revealed distinct shifts in bacterial composition associated with both dietary and pharmacological interventions. Notably, taxa such as Roseburia and Colidextribacter , previously linked to intestinal homeostasis and anti-inflammatory activity, were modulated by ASA and diet, suggesting a microbiome-mediated mechanism of chemoprevention. These findings underscore the independent and complementary roles of diet and pharmacological interventions in CRC prevention, and highlight the gut microbiota as a promising target for future personalised preventive strategies.