Intratumoral microbiome: a crucial regulating factor in development and progression of colorectal cancer

Colorectal cancer (CRC) is one of the most malignant cancers, and studies have indicated that microbes within tumors play a crucial role in CRC. Advanced methodologies, including single-cell and spatial technologies, high-resolution sequencing, and multi-omic integration, are now unraveling the complex composition and function of the intratumoral microbiome. Mechanistically, these microbial communities contribute to CRC initiation by serving as direct mutagens that induce genomic instability, perpetuating a state of chronic inflammation, and activating specific carcinogenic pathways. Furthermore, they actively promote tumor progression and metastatic dissemination through multiple means, including the modulation of key oncogenic signaling pathways, extensive remodeling of the tumor immune microenvironment, and facilitation of a pro-metastatic niche. Given these profound and multifaceted influences, the intratumoral microbiome shows significant promise as a source of diagnostic and prognostic biomarkers, offering considerable potential for non-invasive monitoring and improved risk stratification in clinical practice. Therapeutically, intervention strategies are rapidly evolving, encompassing approaches such as microbiome modulation to enhance conventional therapies, precise clearance of pathogenic bacteria, utilization of intrinsically antitumor microbes, and the engineering of synthetic bacteria as targeted living therapeutics. This review comprehensively outlines the current research methods, elaborates on the mechanistic insights, and discusses the therapeutic targeting of the intratumoral microbiome, aiming to provide a foundational framework for developing new and effective strategies in CRC precision medicine.