Gut Microbiota-Derived Biomarkers for the Non-Invasive Detection of Colorectal Cancer and Adenoma: A Systematic Review

Background/Objectives: Gut microbiota dysbiosis is increasingly implicated in colorectal carcinogenesis, and microbial signatures are emerging as non-invasive diagnostic tools. This systematic review synthesised human studies that evaluated gut microbiota composition, microbiota-derived metabolites and microbial biomarkers for the detection of colorectal cancer (CRC) and colorectal adenoma. Methods: Following the PRISMA 2020 statement, PubMed/MEDLINE, Scopus and the Cochrane Library were searched for studies published between 2015 and 2025, supplemented by Google Scholar and reference-list screening. Human observational and interventional studies reporting microbiota-based diagnostic or associative endpoints were eligible. Data were synthesised narratively, and risk of bias was appraised with QUADAS-2; the protocol was not prospectively registered. Results: Ten studies (5318 participants; nine from East Asia, one from Europe) were included. Four used targeted quantitative PCR, three 16S rRNA sequencing and three shotgun metagenomics, all three combined with metabolomics. Fusobacterium nucleatum and Parvimonas micra were the taxa most frequently enriched in neoplasia (five studies each), together with Peptostreptococcus species, whereas butyrate-producing commensals (Faecalibacterium prausnitzii, Roseburia spp.) were depleted. Multi-omics panels achieved the highest discrimination for CRC (area under the curve [AUC] 0.92–0.994), while performance for adenoma was lower (AUC 0.64–0.91). Adding bacterial markers to the faecal immunochemical test (FIT) increased sensitivity for CRC and advanced adenoma at the cost of specificity. Most studies had a high or unclear risk of bias in the patient-selection and index-test domains, and only two evaluated a screening or mixed symptomatic population. No study reported microbial markers separately for the right colon, left colon and rectum, or for early-onset (<50 years) CRC, and age was often unbalanced between cases and controls. Conclusions: Microbiota-derived biomarkers show reproducible associations with colorectal neoplasia and promising diagnostic accuracy, particularly as adjuncts to FIT, but the evidence derives mainly from small, hospital-based case–control studies in East Asian populations, and accuracy for adenomas remains limited. Site-specific and early-onset data are lacking. Standardised, prospective, multi-ethnic validation studies are required before clinical implementation.