Colorectal cancer (CRC) remains a major global health burden with the gut microbiome emerging as a critical contributor to tumor initiation and progression. Advances in high-throughput sequencing have deepened our understanding of host-microbe interactions across genomic, transcriptomic, epigenomic, and metabolomic levels. This review synthesizes current knowledge on how microbial communities shape colorectal carcinogenesis, including induction of genomic instability, remodeling of host transcriptional and epigenetic landscapes, and reprogramming of metabolic pathways within the tumor microenvironment. Integrative multi-omics strategies and advanced computational tools are powerful means for dissecting these complex biological systems. However, analytical challenges, such as data compositionality, sparsity, and high dimensionality, still hinder meaningful interpretation. Emerging technologies, like long-read sequencing and bacterial single-cell spatial transcriptomics, are enhancing the resolution and accuracy of microbiota profiling. Finally, the convergence of advanced experimental models, artificial intelligence-driven computational integration, and precision microbiome medicine are highlighted as key avenues for translating microbiome insights into preventive, diagnostic, and therapeutic innovations in CRC.
Lu et al. (Mon,) studied this question.