Gut Microbiome Alterations in Colorectal Cancer: Mechanisms, Therapeutic Strategies, and Precision Oncology Perspectives

Abstract

Colorectal cancer (CRC) is one of the most prevalent and lethal oncological diseases worldwide, with a concerning rise in incidence, particularly in developing countries. Recent advances in genetic sequencing have revealed that the gut microbiome plays a crucial role in CRC development. Mechanisms such as chronic inflammation, metabolic alterations, and oncogenic pathways have demonstrated that dysbiosis, a disruption of the gut microbiome, is linked to CRC. Associations have been found between tumor progression, treatment resistance, and pathogenic microbes such as Fusobacterium nucleatum and Escherichia coli. A promising approach for CRC prevention and treatment is microbiome manipulation through interventions such as probiotics, prebiotics, fecal microbiota transplantation, and selective antibiotics. This article explores how gut microbiome alterations influence CRC pathogenesis and examines microbiome modulation strategies currently used as adjuncts to traditional treatments. Advances in artificial intelligence, single-cell and spatial transcriptomics, and large-scale initiatives such as the ONCOBIOME Project are paving the way for the identification of microbiome-derived biomarkers for early CRC detection and personalized treatment. Despite promising progress, challenges such as interindividual variability, causal inference, and regulatory hurdles must be addressed. Future integration of microbiome analysis into multi-omics frameworks holds great potential to revolutionize precision oncology in CRC management.