Gut Microbiome as a Diagnostic Biomarker for Early Cancer Detection: A Systematic Review and Meta-Analysis of 18 Studies across Five Cancer Types

Abstract

BackgroundThe gut microbiome has emerged as a promising non-invasive biomarker for early cancer detection. However, evidence remains fragmented across individual studies with limited cross-cancer comparisons. ObjectivesTo systematically evaluate the diagnostic accuracy of gut microbiome-based signatures across five major cancer types: colorectal cancer (CRC), gastric cancer (GC), pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), and lung cancer (LC). MethodsWe conducted a systematic literature search in PubMed, Embase, and Web of Science (January 2000 - April 2026), following PRISMA 2020 guidelines. Studies reporting area under the receiver operating characteristic curve (AUC) for microbiome-based cancer classification were included. Pooled AUC estimates were derived using a DerSimonian-Laird random-effects model. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). ResultsEighteen studies (2,587 participants) met inclusion criteria. Pooled AUC values were: CRC 0.785 (95%CI 0.750-0.819; I2=30.6%), GC 0.834 (0.781-0.887; I2=56.6%), PDAC 0.853 (0.785-0.921; I2=60.8%), HCC 0.809 (0.747-0.871; I2=70.3%), and LC 0.780 (0.738-0.822; I2=25.0%). Fusobacterium nucleatum was consistently enriched across CRC, GC, and PDAC, while Faecalibacterium prausnitzii and Akkermansia muciniphila were depleted in all five cancer types. Porphyromonas gingivalis showed the highest fold-change in PDAC (log{blacksquare}FC=+2.8). Risk of bias was moderate-to-high in all studies. ConclusionsGut microbiome profiling demonstrates good-to-excellent diagnostic accuracy (AUC 0.78-0.85) across five major cancer types. Shared cross-cancer biomarkers suggest common dysbiotic mechanisms amenable to pan-cancer screening. These findings support integration of microbiome signatures into multi-modal cancer detection platforms.