Endoscopic Swab Sampling as a Novel Method for Gastric Microbiome Profiling: A Feasibility Study Compared with Tissue Biopsy

The gastric microbiome is increasingly recognized in gastric carcinogenesis, extending beyond Helicobacter pylori to oral-associated bacteria. Tissue biopsy is the current standard but is invasive and limited in spatial coverage. This pilot study evaluated an endoscopic swab-based approach as a less invasive alternative. Paired swab and biopsy samples were obtained from the gastric antrum and body of 16 patients undergoing esophagogastroduodenoscopy (32 swabs, 32 biopsies). Microbiome profiling was performed using 16S rRNA V3–V4 amplicon sequencing. Swabs demonstrated higher alpha diversity than biopsies (observed ASVs: 123.5 vs. 48.5, p < 0.001; Shannon index: 4.73 vs. 3.99, p = 0.003). Overall community structures did not differ significantly on robust principal component analysis based on Aitchison distance (p = 0.16 and 0.17, permutational multivariate analysis). Helicobacter was significantly enriched in tissue samples (94.0% vs. 30.7%, log₂ fold change [LFC] = 1.521, q = 0.020), whereas Fusobacterium showed higher abundance in swab samples (LFC = -1.514, q = 0.006). Contamination was minimal. These findings demonstrate that gastric swabs yield microbial profiles comparable to biopsies, with greater diversity and practical advantages. The swab method may provide a non-invasive and reliable alternative for gastric and gastrointestinal microbiome research.