The Gut Microbiome in Early-Onset Colorectal Cancer: Distinct Signatures, Targeted Prevention and Therapeutic Strategies

<b>Background/Objectives:</b> The incidence of early-onset colorectal cancer (EOCRC) is rising worldwide, although its biological and clinical features remain incompletely understood. Emerging evidence implicates gut microbial dysbiosis as a key driver of EOCRC pathogenesis, acting through complex interactions with host genetics, mucosal immunity, and early-life exposures. This review synthesizes current evidence on EOCRC-specific microbial signatures, delineates host-microbiome interactions, and evaluates how these insights may inform precision prevention, early detection, and therapeutic strategies. <b>Methods:</b> A systematic literature search was conducted in PubMed, Scopus, and Web of Science up to August 2025, using combinations of "early-onset colorectal cancer," "gut microbiome," "dysbiosis," and "host-microbiome interactions." Both clinical and preclinical studies were included. Extracted data encompassed microbial composition, mechanistic insights, host-related factors, and microbiome-targeted interventions. Evidence was synthesized narratively to highlight consistent patterns, methodological limitations, and translational implications. <b>Results:</b> EOCRC is consistently associated with enrichment of pro-inflammatory and genotoxic taxa (e.g., <i>Fusobacterium nucleatum</i>, colibactin-producing <i>Escherichia coli</i>, enterotoxigenic <i>Bacteroides fragilis</i>) and depletion of short-chain fatty acid-producing commensals. Multi-omics analyses reveal distinct host-microbiome signatures influenced by germline predisposition, mucosal immunity, sex, and early-life exposures. However, substantial methodological heterogeneity persists. Collectively, these data point to candidate microbial biomarkers for early detection and support the rationale for microbiome-targeted preventive and adjunctive therapeutic approaches. <b>Conclusions:</b> EOCRC harbors unique microbial and host-environmental features that distinguish it from late-onset disease. Integrating host determinants with microbiome signatures provides a framework for precision prevention and tailored therapeutic strategies. Future priorities include harmonizing methodologies, validating microbial biomarkers in asymptomatic young adults, and rigorously testing microbiome-targeted interventions in clinical trials.