{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:41:17Z","timestamp":1793814077780,"version":"4.6.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004457","name":"The World Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004457","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"\n Background<\/jats:title>\n \n Helicobacter pylori<\/jats:italic>\n contributes to gastric carcinogenesis through diverse virulence mechanisms, transcriptional plasticity, and rising antimicrobial resistance. However, how these features integrate into coordinated bacterial states within the tumor microenvironment remains unclear. This study integrates virulence, expression, and antimicrobial signatures to define potentially meaningful\n H. pylori<\/jats:italic>\n profiles.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We analyzed 159 histologically confirmed,\n H. pylori<\/jats:italic>\n -positive gastric cancer tissues. Virulence gene presence, expression, and antimicrobial resistance\u2013associated mutations were quantified using polymerase chain reaction\u2013based assays. Twenty-one molecular features were standardized and integrated using unsupervised\n k<\/jats:italic>\n -means and TwoStep clustering. Associations with clinicopathological characteristics were evaluated using false-discovery-rate-adjusted statistical tests.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Two dominant\n H. pylori<\/jats:italic>\n molecular states were identified: a virulence-competent Colonizer profile (127\/158, 80.4%) enriched for\n cagA<\/jats:italic>\n \/\n vacA<\/jats:italic>\n gene carriage and expression (\n q<\/jats:italic>\n \u00a0&lt;\u00a00.001), and a putative Resistant Inflammatory profile (31\/158, 19.6%) characterized by elevated\n iceA<\/jats:italic>\n expression (\n q<\/jats:italic>\n \u00a0=\u00a00.002) and clarithromycin resistance mutations (\n q<\/jats:italic>\n \u00a0=\u00a00.022), with reduced\n cagA<\/jats:italic>\n \/\n vacA<\/jats:italic>\n (\n q<\/jats:italic>\n \u00a0&lt;\u00a00.001). Histological detectability of\n H. pylori<\/jats:italic>\n differed markedly between profiles (91.3% vs 45.2%,\n p<\/jats:italic>\n \u00a0&lt;\u00a00.001). Univariate differences were observed in tumor differentiation (\n p<\/jats:italic>\n \u00a0=\u00a00.047) and anatomical distribution (\n p<\/jats:italic>\n \u00a0=\u00a00.042), while multivariable associations were directional but non-significant. Four-cluster modelling identified additional sub-phenotypes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Integrated profiling suggests that\n H. pylori<\/jats:italic>\n adopts distinct molecular states in gastric cancer associated with specific clinicopathological features. These findings support systems-level microbial characterization as a hypothesis-generating framework for exploring whether microbial molecular states may contribute to future risk stratification and eradication strategies in AMR-endemic regions, pending functional and external validation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1812371","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:43:14Z","timestamp":1779169394000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrated virulence\u2013resistance profiling of Helicobacter pylori reveals context-dependent pathogenic signatures in gastric cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Oliver","family":"Mbuthia","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, College of Health Sciences, University of Nairobi","place":["Nairobi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azhar","family":"Mehmood","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad","place":["Islamabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishrat","family":"Mahjabeen","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad","place":["Islamabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmood A.","family":"Kayani","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad","place":["Islamabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jael","family":"Obiero","sequence":"additional","affiliation":[{"name":"Department of Reproductive Health and Biology, Kenya Institute of Primate Research","place":["Karen, Nairobi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University","place":["Yufu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefa","family":"Bosire","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacognosy, College of Health Sciences, University of Nairobi","place":["Nairobi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne W.","family":"Mureithi","sequence":"additional","affiliation":[{"name":"KAVI \u2013 Institute of Clinical Research, College of Health Sciences, University of Nairobi","place":["Nairobi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/s41065-025-00616-z","article-title":"Integrative analysis of Helicobacter pylori-driven stomach adenocarcinoma reveals epigenetic deregulation, immune evasion, and therapeutic resistance","volume":"163","author":"Alissa","year":"2025","journal-title":"Hereditas"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2025.107864","article-title":"Helicobacter pylori associated MicroRNA and transcriptional networks in gastric pathogenesis: Exploring the epigenetic dialogue landscape","volume":"207","author":"Alva","year":"2025","journal-title":"Microb. 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