Frontiers in Oncology · Oct 30, 2026
Unlocking Microbiome Secrets: A Systematic Review of Microbiome-Derived Biomarkers for Early Colorectal Cancer Detection
By Juliana Victoria Martinez Janne, Mabel Bohorquez Lozano, Shehnaz K Hussain
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and established non-invasive screening tools such as the guaiac fecal occult blood test and the fecal immunochemical test have limited sensitivity for early-stage disease. Microbiome-derived biomarkers have emerged as a promising alternative for early, non-invasive CRC detection. This systematic review evaluated the diagnostic performance of microbiome-derived biomarkers - including 16S rRNA gene sequencing, metagenomic shotgun sequencing, and co-metabolomic profiling - for detecting early-stage colorectal cancer and its precursor lesions. A systematic search of PubMed and EMBASE (via OVID) covering the ten years up to May 3, 2024 was conducted following PRISMA 2020 guidelines, with triplicate ASReview-assisted screening and two-of-three reviewer consensus for full-text selection; risk of bias was assessed using QUADAS-2. Of 3,859 records identified in the primary search, 26 studies met all eligibility criteria; following a post-hoc bibliographic verification and a subsequent targeted search update, the final set comprised 28 studies, drawn from East Asia, South Asia, Europe, and North America and predominantly using fecal samples, with a minority also using oral swab or serum samples. Reported diagnostic performance varied widely across studies (area under the curve 0.28-0.98; sensitivity 18-100%; specificity 39-97%), with the highest accuracy reported for panels derived from oral swab samples. Most studies carried a high or unclear risk of bias in the index-test domain, and no included study reported independent external validation of its biomarker panel in a separate cohort. Microbiome-derived biomarkers show promising but highly heterogeneous and largely unvalidated diagnostic performance for early CRC detection. Standardized sample-collection and analytic protocols, together with externally validated, multi-center studies in populations not yet represented in the evidence base - including South America - are needed before these biomarkers can be considered for clinical or population-level screening use.