Characterization of the Oral and Stomach Microbial Community Structure in Patients with Intestinal Metaplasia, Dysplasia, and Gastric Cancer Through High-Throughput Sequencing

Gastric cancer (GC) is the fifth most common cancer worldwide, with the highest incidence in East Asia. Although <i>H. pylori</i> is a well-known risk factor, carcinogenesis can occur independently of <i>H. pylori</i> infection, and approximately 43% of adults carry <i>H. pylori</i> as part of their native microbiota. This study aimed to identify potential oral and gastric microbial markers across different histological stages of GC in both <i>H. pylori</i>-positive and -negative patients. Buccal swabs and gastric mucosa samples were collected from patients with intestinal metaplasia, low-grade dysplasia, high-grade dysplasia, early GC, or advanced GC. Total DNA was extracted, and 16S rRNA gene amplicon sequencing was performed. Microbiome diversity generally remained stable across histological stages, with no directional shifts in community structure. Differential abundance analysis revealed higher relative abundances of <i>Anaerostipes</i>, <i>Phocaeicola</i>, and <i>Collinsella</i> in the gastric antrum of cancerous samples. <i>Anaerostipes</i> and <i>Phocaeicola</i> are typically enriched in the intestinal microbiota but are rarely observed in the stomach, suggesting their potential ecological and pathological relevance in gastric carcinogenesis. In <i>H. pylori</i>-negative patients, however, a different stage-associated abundance pattern was observed, in which <i>Faecalibacterium</i>, a genus predominantly associated with the intestinal environment, was less abundant in advanced gastric cancer samples than in earlier histological stages within the gastric body. These findings suggest that microbial changes during gastric cancer progression may follow different trajectories depending on <i>H. pylori</i> infection status. In oral samples, <i>Haemophilus</i> and <i>Prevotella</i> were more abundant in intestinal metaplasia than in low-grade dysplasia, and network analysis indicated links between <i>Neisseria</i> and <i>Filifactor</i> at oral and gastric sites. However, as the study population was limited to a single country and ethnicity, the applicability of these microbial markers should be carefully considered.