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

Abstract

Background/Objectives: 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. Methods: 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. Results: EOCRC is consistently associated with enrichment of pro-inflammatory and genotoxic taxa (e.g., Fusobacterium nucleatum, colibactin-producing Escherichia coli, enterotoxigenic Bacteroides fragilis) 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. Conclusions: 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.