The intratumoral microbiome in colorectal cancer: origins, microenvironmental interactions, and new horizons in precision medicine

As a key functional component of the tumor microenvironment (TME), the intratumoral microbiome in colorectal cancer (CRC) has revolutionized the traditional paradigm of the “sterile tumor.” Far from being mere “bystanders,” these intratumoral microbes act as key drivers deeply implicated in remodeling the TME, influencing tumor progression, and determining therapeutic responses, thus necessitating a comprehensive synthesis of their complex biological characteristics and potential for clinical translation. Therefore, this review systematically summarizes the potential origins, community characteristics, and anatomical heterogeneity of the intratumoral microbiome. It further explores the precise mechanisms driving tumor progression, including the induction of genomic instability, metabolic reprogramming, epigenetic regulation, and immune microenvironment remodeling. We highlight the clinical utility of intratumoral microbes in CRC diagnosis, prognosis, and therapeutic prediction, while also introducing novel intervention strategies based on nanomedicine, engineered probiotics, and phage therapy. Finally, critical challenges such as contamination control in low-biomass samples, sampling heterogeneity, and the delineation of causality are scrutinized, aiming to provide new perspectives for the development of microbiome-guided precision medicine in CRC.