{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:37:57Z","timestamp":1783996677146,"version":"3.55.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["P30-ES002109"],"award-info":[{"award-number":["P30-ES002109"]}]},{"name":"HHS | National Institutes of Health","award":["P01CA28842"],"award-info":[{"award-number":["P01CA28842"]}]},{"name":"HHS | National Institutes of Health","award":["R35 CA210088"],"award-info":[{"award-number":["R35 CA210088"]}]},{"name":"HHS | National Institutes of Health","award":["1R01CA281732-01"],"award-info":[{"award-number":["1R01CA281732-01"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,1,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Helicobacter pylori<\/jats:italic>\n            (\n            <jats:italic>H. pylori<\/jats:italic>\n            ) causes a cascade from gastritis to gastric neoplasia. During the chronic stages, the oncogenic transcription factor forkhead box protein M1 (\n            <jats:italic>FOXM1<\/jats:italic>\n            ) becomes increasingly expressed. Given certain strains of the gastric commensal\n            <jats:italic>Cutibacterium acnes<\/jats:italic>\n            (\n            <jats:italic>C. acnes<\/jats:italic>\n            ) produce thiopeptides that directly inhibit FOXM1, we hypothesized that coinfection with thiopeptide-positive\n            <jats:italic>C. acnes<\/jats:italic>\n            would decrease\n            <jats:italic>Foxm1<\/jats:italic>\n            expression and alter\n            <jats:italic>H. pylori<\/jats:italic>\n            -induced pathogenesis.\n            <jats:italic>C. acnes<\/jats:italic>\n            was isolated from 31% of gastric biopsies from Nicaraguan patients, and thiopeptide-positive strains were identified by whole genome sequencing. Germ-free INS-GAS mice were inoculated with thiopeptide-positive\n            <jats:italic>C. acnes<\/jats:italic>\n            ,\n            <jats:italic>H. pylori<\/jats:italic>\n            SS1,\n            <jats:italic>H. pylori<\/jats:italic>\n            1 week before\n            <jats:italic>C. acnes<\/jats:italic>\n            ,\n            <jats:italic>C. acnes<\/jats:italic>\n            2 weeks before\n            <jats:italic>H. pylori<\/jats:italic>\n            , or no bacteria. At 17 weeks post-infection, males dosed with\n            <jats:italic>C. acnes<\/jats:italic>\n            followed by\n            <jats:italic>H. pylori<\/jats:italic>\n            exhibited increased inflammation scores by histopathology; however, males dosed with\n            <jats:italic>H. pylori<\/jats:italic>\n            followed by\n            <jats:italic>C. acnes<\/jats:italic>\n            exhibited reduced gastric\n            <jats:italic>Foxm1<\/jats:italic>\n            , pro-inflammatory cytokine (\n            <jats:italic>Il-1\u03b2<\/jats:italic>\n            ,\n            <jats:italic>Ifn-\u03b3<\/jats:italic>\n            ,\n            <jats:italic>Tnf-\u03b1<\/jats:italic>\n            ,\n            <jats:italic>Il-17a<\/jats:italic>\n            , and\n            <jats:italic>iNOS<\/jats:italic>\n            ), regulatory cytokine (\n            <jats:italic>Foxp3<\/jats:italic>\n            ) gene expression, pro-inflammatory IgG2a antibodies, and gastric lymph node ROR\u03b3T expression compared to\n            <jats:italic>H. pylori-<\/jats:italic>\n            monoinfected mice. Male mice coinfected with\n            <jats:italic>C. acnes<\/jats:italic>\n            followed by\n            <jats:italic>H. pylori<\/jats:italic>\n            exhibited reduced gastric inflammatory markers (IL-17, IL-10, GM-CSF, M-CSF, MCP-1, MIP-1\u03b1, MIP-2, RANTES, and VEGF) by cytokine array analysis and reduced\n            <jats:italic>H. pylori<\/jats:italic>\n            gastric colonization. These data show that thiopeptide-positive\n            <jats:italic>C. acnes<\/jats:italic>\n            exhibited anti-inflammatory and anti-FOXM1 properties in the context of\n            <jats:italic>H. pylori<\/jats:italic>\n            gastritis.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>H. pylori<\/jats:italic>\n              infects half of the world population and is the leading cause of gastric cancer. We previously demonstrated that gastric cancer risk is associated with gastric microbiota. Specifically, gastric urease-positive\n              <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n              and\n              <jats:italic>Streptococcus salivarius<\/jats:italic>\n              had contrasting effects on\n              <jats:italic>H. pylori<\/jats:italic>\n              -associated gastric pathology and immune responses in germ-free INS-GAS mice. As gastritis progresses to gastric cancer, the oncogenic transcription factor\n              <jats:italic>Foxm1<\/jats:italic>\n              becomes increasingly expressed. In this study, we evaluated the gastric commensal\n              <jats:italic>C. acnes<\/jats:italic>\n              , certain strains of which produce thiopeptides that directly inhibit FOXM1. Thiopeptide-positive\n              <jats:italic>C. acnes<\/jats:italic>\n              was isolated from Nicaraguan patient gastric biopsies and inoculated into germ-free INS-GAS mice with\n              <jats:italic>H. pylori<\/jats:italic>\n              . We, therefore, asked whether coinfection with\n              <jats:italic>C. acnes<\/jats:italic>\n              expressing thiopeptide and\n              <jats:italic>H. pylori<\/jats:italic>\n              would decrease gastric\n              <jats:italic>Foxm1<\/jats:italic>\n              expression and pro-inflammatory cytokine mRNA and protein levels. Our study supports the growing literature that specific non-\n              <jats:italic>H<\/jats:italic>\n              .\n              <jats:italic>pylori<\/jats:italic>\n              gastric bacteria affect inflammatory and cancer biomarkers in\n              <jats:italic>H. pylori<\/jats:italic>\n              pathogenesis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.03450-23","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T14:01:55Z","timestamp":1701180115000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Gastric coinfection with thiopeptide-positive\n            <i>Cutibacterium acnes<\/i>\n            decreases FOXM1 and pro-inflammatory biomarker expression in a murine model of\n            <i>Helicobacter pylori<\/i>\n            -induced gastric cancer"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4070-8824","authenticated-orcid":false,"given":"Courtney","family":"Lunger","sequence":"first","affiliation":[{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeli","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilda","family":"Holcombe","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6112-0546","authenticated-orcid":false,"given":"Anthony J.","family":"Mannion","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn","family":"Dzink-Fox","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Kurnick","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sureshkumar","family":"Muthupalani","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian E.","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith T.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Peek","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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