Combination of a pesco vegetarian diet with non-steroidal anti-inflammatory drugs reduces colorectal cancer risk and modulates gut microbiota in PIRC rats.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with genetic predispositions such as Familial Adenomatous Polyposis (FAP) contributing significantly to early-onset disease. This study investigated the synergic 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 (800 and 1600 ppm) or a single low dose of SU (80 ppm), and tumour 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 chemoprevention although mechanistic effect still need to be understood. 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.