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 ( I 2 = 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.
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Hu et al. (2026) studied this question.
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