Noninvasive early detection of colorectal cancer through gut microbiome-derived biomarkers

Colorectal cancer (CRC) remains a major global burden, with 1.9 million new cases and 935000 deaths reported in 2024. Despite available screening tools, nearly 45% of cases are still diagnosed at advanced stages, where the 5-year survival rate falls below 14%, compared to >90% in early detection. The limitations of colonoscopy its invasiveness, cost, and poor compliance (<40% globally) demand innovative, noninvasive diagnostic solutions. Gut microbiome profiling has recently emerged as a transformative approach, with specific bacterial signatures such as Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus anaerobius showing AUC values between 0.85 and 0.93 for early CRC identification. Integrating metagenomic and metabolomic data enhances diagnostic accuracy to 89% sensitivity and 91% specificity. Moreover, altered microbial metabolites including decreased short-chain fatty acids and elevated secondary bile acids correlate with a 2.3- to 3.1-fold higher risk of carcinogenesis. Novel CRISPR-Cas13a-based assays further allow sub-attomolar detection of microbial RNA transcripts, underscoring a new frontier in microbiome-driven cancer diagnostics. Collectively, gut microbiome-derived biomarkers represent a noninvasive, mechanistically grounded, and highly sensitive platform for early CRC detection with significant translational potential.