Modulating Strategies of the Intestinal Microbiota in Colorectal Cancer García Mansilla, María José Rodríguez Sojo, María Jesús Lista, Andreea Roxana Ayala Mosqueda, Ciskey Vanessa García García, Jorge Gálvez Peralta, Julio Juan Rodríguez Nogales, Alba Ruiz Malagón, Antonio Jesús Rodríguez Sánchez, María José microbiota Colorectal cancer Therapeutic approaches Background/Objectives: Colorectal cancer (CRC) accounts for nearly 10% of global cancer cases and is the second leading cause of cancer-related mortality. While age and genetics are non-modifiable risk factors, nutrition and its impact on gut microbiota are emerging as key determinants in CRC prevention and management. We aimed to systematically evaluate recent evidence on the role of diet and microbiota-targeted interventions—including probiotics, prebiotics, synbiotics, and postbiotics—in modulating CRC risk and therapeutic outcomes. Methods: A structured literature search was performed in PubMed, ResearchGate, Scopus, and ScienceDirect up to July of 2025. Reference lists of relevant reviews and clinical trials were also screened. A total of 36 studies were selected according to PRISMA guidelines. Data were extracted on dietary exposures, microbiota modulation, metabolite profiles, and CRC-related outcomes. Evidence quality was assessed using appropriate appraisal tools for observational and interventional designs. Results: Western-type diets were consistently associated with microbiota dysbiosis, the enrichment of pro-inflammatory and genotoxic taxa, and elevated CRC risk. Diets rich in fiber and polyphenols enhanced commensals producing short-chain fatty acids (e.g., butyrate), with anti-inflammatory and antineoplastic effects. Probiotics, prebiotics, and postbiotics demonstrated potential to restore microbial balance, improve epithelial integrity, and enhance tolerance to conventional therapies. Conclusions: Current evidence supports a complex interplay between nutrition, the gut microbiota, and CRC, with strong translational potential. Microbiota-modulating nutritional strategies, particularly fiber-rich diets and synbiotics, show the most consistent microbiota-related benefits in CRC prevention and represent promising adjuncts to standard therapies. However, much of the available research is still based on preclinical models. Therefore, there is a pressing need for well-designed clinical studies in human populations to validate these findings and inform evidence-based guidelines. 2025-11-21T10:15:06Z 2025-11-21T10:15:06Z 2025-11-14 journal article García Mansilla, M.J.; Rodríguez Sojo, M.J.; Roxana Lista, A.; Ayala Mosqueda, C.V.; García García, J.; Gálvez Peralta, J.; Rodríguez Nogales, A.; Ruiz Malagón, A.J.; Rodríguez Sánchez, M.J. Modulating Strategies of the Intestinal Microbiota in Colorectal Cancer. Nutrients 2025, 17, 3565. https://doi.org/10.3390/nu17223565 https://hdl.handle.net/10481/108173 10.3390/nu17223565 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI