Distinct signatures in the human gut and oral microbiomes of gastric cancer

Microbiome dysbiosis is increasingly recognized as a hallmark of gastric cancer (GC). Here, we analyzed gut and oral shotgun metagenomic data from 317 individuals across two independent cohorts, with validation in a Harbin cohort. We identify 20 oral-gut shared species enriched in the gut of GC, predominantly lactic acid bacteria (LAB). While most gut microbial markers are abundant in saliva, none are significantly altered in GC. Strain-level analysis of 87 matched saliva-stool metagenomes confirms oral-gut transmission of Streptococcus species. GC-enriched LAB form robust co-abundance networks in oral and gut microbiomes, suggesting synergistic interactions. Functional analysis reveals enriched lactate fermentation pathways in GC stool, aligning with LAB dominance and previous findings on gastric microbiota. Moreover, microbiome-based classifiers achieve high predictive accuracy (area under receiver operating characteristic curve [AUROC] = 0.85 for stool, 0.87 for saliva) for GC diagnosis, highlighting translational potential. Collectively, these findings underscore the critical role of the oral-gut microbiome axis in GC.