Dual-microbial signature as a predictor of postoperative colorectal cancer recurrence.

3611 Background: Current surveillance strategies for postoperative recurrence in colorectal cancer predominantly depend on tumor markers, imaging modalities, and endoscopic procedures; however, these approaches are challenged by suboptimal diagnostic accuracy. Consequently, the identification and validation of novel biomarkers represent an urgent clinical necessity. Sensitive microbiome-based approaches for postoperative risk stratification, surveillance optimization, and early recurrence detection may substantially influence clinical decision-making and resource allocation for colorectal cancer patients. Methods: This cohort study included CRC fecal and tumor samples from four independent cohorts (n = 615) in the Fudan University Shanghai Cancer Centre (Shanghai, China) between January 2017 and December 2020, with follow-up through December 2024. Fecal samples from the discovery (n = 250), training-validation cohorts (n = 153), as well as tumors with paired adjacent normal tissues from the investigation cohort (n = 244), were subjected to multi-omics analyses. We developed prediction models of disease-free survival by additionally incorporating dual-microbial signature including the abundance of Roseburia and Bifidobacterium. Both models were evaluated by internal validation cohort, and visual nomograms of prediction models were constructed accordingly. Results: We found that the combined high abundance of Roseburia and Bifidobacterium was associated with favorable outcomes (P = 0.039), especially in male (P = 0.018) and early-onset colorectal cancer (P = 0.047). Integration of clinical variables with a dual-microbial signature achieved a mean AUC > 0.8 for recurrence prediction. A high combined abundance of Roseburia and Bifidobacterium was linked to reduced enrichment of primary bile acid biosynthesis pathways and increased enrichment of propanoate metabolism pathways. Conclusions: This study proposes a novel strategy for CRC recurrence risk assessment and highlights the potential of gut microbiota as a tertiary preventive approach in CRC management. However, the proposed model has not yet been implemented in clinical practice and requires validation in large, multicenter prospective cohorts before clinical translation.