Oral and Fecal Microbial Dysbiosis as Non-Invasive Diagnostic Biomarkers for Gastrointestinal Cancers: A Systematic Review and Meta-Analysis of Diagnostic Accuracy.

Abstract

Gastrointestinal (GI) cancers, including esophageal (EC), gastric (GC), and colorectal cancer (CRC), impose a substantial global burden, with early detection remaining crucial for improving patient outcomes. The oral and gut microbiota are increasingly implicated in cancer development and hold promise as sources of non-invasive biomarkers. However, current evidence on microbiome-based diagnostics remains fragmented, and a systematic comparison of the diagnostic accuracy between oral and fecal sampling across multiple GI cancer types is lacking. To address this gap, a systematic search of PubMed, Embase, and Scopus up to December 31, 2025, identified 43 case-control studies (59 cohorts) comprising 4452 cancer patients and 5809 controls. The pooled area under the curve (AUC) was 0.846 (95% CI: 0.824-0.867), though with substantial heterogeneity (I² = 86.5%). By cancer type, pooled AUCs were 0.746 for EC (5 cohorts), 0.886 for GC (8 cohorts), and 0.850 for CRC (46 cohorts). A bivariate analysis of 20 cohorts comparing sample types found no statistically significant difference in diagnostic performance between oral (sAUC = 0.863) and fecal sampling (sAUC = 0.820; p = 0.369). While these exploratory findings suggest that oral and fecal microbial biomarkers may offer comparable diagnostic accuracy for GI cancers, with oral sampling presenting a more practical option for screening, the results are preliminary. Significant heterogeneity, a limited number of oral cohorts, and the absence of clinical control groups highlight the need for large-scale prospective studies with direct comparisons and real-world validation to validate these biomarkers for clinical translation.