Fuente: PubMed "microbial biotechnology" mBio. 2026 Jul 31:e0158926. doi: 10.1128/mbio.01589-26. Online ahead of print.ABSTRACTGastric 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.IMPORTANCEThe gastric microbiota plays a critical role in gastrointestinal health and disease. However, the ecological interactions between Helicobacter pylori and non-H. pylori bacteria remain poorly understood. Among established bacterial pathogens linked to gastric carcinogenesis, H. pylori and Streptococcus anginosus are recognized as major contributors. In this study, we systematically evaluated infection patterns and potential associations between these two pathogens using public metagenomic data sets and qPCR analysis of clinical samples (feces and gastric fluid) from multicenter cohorts. We found no significant association between their infection statuses (P > 0.05), indicating independent colonization patterns and likely differences in their pathogenic mechanisms within the human host. Complementary in vitro and cellular analyses further showed that H. pylori primarily acts through direct mucosal colonization and virulence factors, whereas S. anginosus influences host responses mainly via its metabolic products. These findings demonstrate that H. pylori and S. anginosus operate through distinct colonization strategies and pathogenic pathways. They underscore the importance of accounting for mechanistic heterogeneity in gastric microbiome research and provide a conceptual framework for future investigations into microbe-driven pathogenesis of gastric disease.PMID:42535843 | DOI:10.1128/mbio.01589-26