Distinct microbial signatures of liquid biopsy samples during gastric carcinogenesis and insights from extracellular vesicle analysis

Abstract

Background/Aims: The early detection of gastric cancer is crucial for improving patient outcomes. However, its pathogenesis is not fully understood. The microbiome and extracellular vesicles (EVs) might play a role in gastric carcinogenesis. We aimed to identify gastric-carcinogenesis-associated microbial signatures and evaluate whether these features vary across disease stages. Methods: We enrolled 141 participants (132 patients with gastric cancer or dysplasia and 9 healthy controls). Microbial-de-rived EVs were isolated from gastric juice, saliva, serum, and urine. Next-generation sequencing of EV-derived bacterial DNA was performed. Results: This sequencing revealed the alpha and beta diversities and microbial composition across different disease stages. The alpha diversity was significantly increased in the gastric juice and serum of disease groups. The beta diversity showed significant differences among patient groups. Distinct microbial signatures were observed across different disease stages in all four sample types. Specific bacterial species––Cutibacterium acnes, Streptococcus oralis, Pseudomonas antarctica, Ralstonia insidiosa, and Pseudomonas yamanorum––exhibited unique abundance patterns associated with disease progression, suggesting their potential as noninvasive biomarkers. Conclusions: Changes in microbial diversity and distinct microbial signatures were observed during gastric carcinogenesis in both gastric juice and extragastric samples, indicating the potential of microbial-derived EVs from liquid biopsy samples as biomarkers for gastric cancer.