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 , and 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.