Author Identifier (ORCID)
Abstract
Gastric cancer remains a major global health burden, ranking fifth worldwide in both incidence and mortality. While Helicobacter pylori is a well-established Group I carcinogen, increasing evidence suggests that non-H. pylori bacteria, including Streptococcus anginosus, may also contribute to gastric carcinogenesis. However, their comparative pathogenic roles and interactions remain poorly defined. In this study, public databases showed stage-dependent abundance changes of H. pylori and S. anginosus but no significant correlation during gastric cancer progression. We further quantified both bacteria in gastric fluid samples collected from 500 individuals using a non-invasive gastric string test and in fecal samples from an independent cohort of 500 individuals by qPCR. In the two cohorts, no significant correlations were observed between the two bacterial pathogens, suggesting distinct colonization and pathogenic patterns. To evaluate functional differences, AGS cell co-culture models were established to explore their pro-tumorigenic effects. H. pylori predominantly exerted tumor-promoting effects through bacterial cell-associated mechanisms, whereas S. anginosus exerted stronger pro-tumorigenic effects via its metabolites. In particular, transcriptomic analysis revealed that proliferation-associated genes, including DEK and RTF1, were significantly upregulated by 21.9-fold and 19.2-fold, respectively, in cells treated with Streptococcus anginosus metabolite (SAM). Metabolomic profiling of SAM identified increased levels of spermidine and polyamine-related metabolites. Among these, N-acetylcadaverine, N-acetyltyrosine, N-acetyltryptophan, and urocanic acid were experimentally validated to significantly promote AGS cell proliferation. Collectively, these findings demonstrate that H. pylori and S. anginosus drive gastric tumorigenesis through contact-dependent and metabolite-mediated mechanisms, respectively, highlighting bacterial metabolites as emerging contributors to gastric cancer progression.
Keywords
AGS cells, gastric cancer, Helicobacter pylori, metabolomics, Streptococcus anginosus, transcriptomics
Document Type
Journal Article
Date of Publication
7-13-2026
E-ISSN
21507511
ISSN
21612129
Volume
17
Issue
9
PubMed ID
42535843
Publication Title
mBio
Publisher
American Society for Microbiology
School
School of Medical and Health Sciences
RAS ID
101956
Funding Information
This study was financially supported by the Research Foundation for Advanced Talents of Guangdong Provincial People’s Hospital (grant no. KY012023293, recipient: L.W.), the National Natural Science Foundation of China (grant no. 82372258, recipient: L.W.), and the Young Top-Talent in Science and Technology Innovation of Guangdong Special Support Program (grant no. 2025TQ09A269, recipient: L.W.).
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
First Page
1
Last Page
20
Recommended Citation
Luan, L., Song, X., Zeng, Y., Xie, Y., Hong, Y., Tang, J., Ma, C., Gu, B., & Wang, L. (2026). Differential pro-tumorigenic effects of Helicobacter pylori and Streptococcus anginosus on AGS cells: Contact-dependent versus metabolite-driven mechanisms. mBio, 17(9), Article e0158926. https://doi.org/10.1128/mbio.01589-26