Clinical applications of gut microbiome for non-invasive diagnosis of colorectal neoplasia

Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related death worldwide. While screening programs have reduced mortality, current stool-based tests such as the faecal immunochemical test (FIT) and tumour marker assays, remain limited in sensitivity for adenoma detection and rely on relatively later-stage biological signals in the carcinogenic process. False positives lead to unnecessary invasive procedures, whilst missed adenomas continue to progress, highlighting the need for alternative strategies. Accumulating evidence implicates the gut microbiome in CRC pathogenesis, which involves tumour-associated dysbiosis and microbial ecosystem shifts. Multinational metagenomic studies have consistently identified reproducible microbial signatures that can serve as biomarkers of disease and may predate the biological signals used in conventional screening. PCR-based microbial markers have emerged as practical tools for clinical application, enabling sensitive and specific detection of adenomas and CRC. A recent microbial panel incorporating Fusobacterium nucleatum, Hungatella hathewayi, Christensenella hongkongensis, and a novel bacterial gene marker m3 from Lachnoclostridium demonstrated improved sensitivity for adenomas whilst maintaining comparable accuracy for CRC. International guidelines have begun to recommend combining microbiome-based assays with FIT into integrated screening programs that target multiple biologic processes across the pathogenesis. Microbiome-based stool testing represents a promising non-invasive approach that improves detection of adenomas in early-stage disease, often missed by FIT alone and could enable more refined risk stratification. Further validation across diverse populations, assessment of cost-effectiveness, and integration into established screening infrastructures will be critical for broad clinical adoption.