Harnessing gut microbiota for colorectal cancer therapy: from clinical insights to therapeutic innovations

Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality worldwide, yet improvements in survival have been modest despite advances in conventional therapies. The gut microbiota has emerged as a critical player in CRC pathogenesis and a promising therapeutic target to enhance clinical outcomes. Mounting evidence implicates specific microorganisms, notably Escherichia coli, Fusobacterium nucleatum, and Bacteroides fragilis, in tumor initiation and progression through DNA damage, inflammatory modulation, and immunosuppressive mechanisms. Clinical trials investigating microbiome modulators—including faecal microbiota transplantation, probiotics, prebiotics, and engineered biotherapeutics—highlight their potential to augment chemotherapy, radiotherapy, immunotherapy, and surgical recovery, with encouraging preliminary efficacy in treatment-resistant CRC subtypes. Nonetheless, translating microbiome interventions into standardized clinical practice requires rigorous mechanistic validation, robust biomarker development, and careful management of safety concerns. Future research must focus on integrating high-resolution multi-omics, spatial microbiome mapping, artificial intelligence analytics, and innovative microbiome-targeted nanotechnologies to precisely reshape gut microbial communities, thereby ushering in a new era of precision oncology in colorectal cancer management.