{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:59:54Z","timestamp":1789207194299,"version":"build-2803163510"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Gastric cancer remains a major global health burden, ranking fifth worldwide in both incidence and mortality. While\n                      <jats:italic toggle=\"yes\">Helicobacter pylori<\/jats:italic>\n                      is a well-established Group I carcinogen, increasing evidence suggests that non-\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      bacteria, including\n                      <jats:italic toggle=\"yes\">Streptococcus anginosus<\/jats:italic>\n                      , 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\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                      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.\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      predominantly exerted tumor-promoting effects through bacterial cell-associated mechanisms, whereas\n                      <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                      exerted stronger pro-tumorigenic effects via its metabolites. In particular, transcriptomic analysis revealed that proliferation-associated genes, including\n                      <jats:italic toggle=\"yes\">DEK<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">RTF1<\/jats:italic>\n                      , were significantly upregulated by 21.9-fold and 19.2-fold, respectively, in cells treated with\n                      <jats:italic toggle=\"yes\">Streptococcus anginosus<\/jats:italic>\n                      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\n                      <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                      drive gastric tumorigenesis through contact-dependent and metabolite-mediated mechanisms, respectively, highlighting bacterial metabolites as emerging contributors to gastric cancer progression.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The gastric microbiota plays a critical role in gastrointestinal health and disease. However, the ecological interactions between\n                        <jats:italic toggle=\"yes\">Helicobacter pylori<\/jats:italic>\n                        and non-\n                        <jats:italic toggle=\"yes\">H<\/jats:italic>\n                        .\n                        <jats:italic toggle=\"yes\">pylori<\/jats:italic>\n                        bacteria remain poorly understood. Among established bacterial pathogens linked to gastric carcinogenesis,\n                        <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">Streptococcus anginosus<\/jats:italic>\n                        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 (\n                        <jats:italic toggle=\"yes\">P<\/jats:italic>\n                        &gt; 0.05), indicating independent colonization patterns and likely differences in their pathogenic mechanisms within the human host. Complementary\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        and cellular analyses further showed that\n                        <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                        primarily acts through direct mucosal colonization and virulence factors, whereas\n                        <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                        influences host responses mainly via its metabolic products. These findings demonstrate that\n                        <jats:italic toggle=\"yes\">H. pylori<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">S. anginosus<\/jats:italic>\n                        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.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01589-26","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T13:00:49Z","timestamp":1785502849000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Differential pro-tumorigenic effects of\n                    <i>Helicobacter pylori<\/i>\n                    and\n                    <i>Streptococcus anginosus<\/i>\n                    on AGS cells: contact-dependent versus metabolite-driven 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