Microbiome-Shaped Metastatic Niches in Colorectal Cancer: Organ-Specific Patterns, Immune-Metabolic Mechanisms, and Therapeutic Translation.

Despite advances in systemic therapies, metastatic colorectal cancer (mCRC) remains largely incurable, underscoring persistent gaps in our understanding of metastatic progression and therapeutic resistance. Emerging evidence suggests that gut and tumor-associated microbial communities may contribute to metastatic progression by shaping organ-specific niches, disrupting intestinal and vascular barriers, remodeling immune and stromal microenvironments, and altering host-microbial metabolism. This review synthesizes current evidence on the involvement of gut and intratumoral microbial communities in colorectal cancer metastasis, with emphasis on liver, lung, lymphatic, and peritoneal metastatic patterns; microbial translocation and barrier dysfunction; microbiome-tumor microenvironment interactions; and metabolic pathways such as bile acid, short-chain fatty acid, and tryptophan metabolism. Furthermore, distinct microbial signatures have been associated with responses to chemotherapy, radiotherapy, immunotherapy, and targeted therapies, supporting their potential value as candidate biomarkers for treatment stratification and prognosis, particularly when interpreted alongside treatment exposure and longitudinal microbiome dynamics. Finally, we discuss microbiome-targeted interventions as emerging adjunctive strategies that may help modulate treatment response, while emphasizing the need for standardized, longitudinal, and mechanistically validated studies before clinical translation in mCRC.