{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:30:47Z","timestamp":1788813047499,"version":"build-2803163510"},"reference-count":22,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan society for the promotion of science","award":["21K07336"],"award-info":[{"award-number":["21K07336"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Helicobacter pylori infection is an important risk factor for developing gastric cancer. However, only a few H. pylori-infected people develop gastric cancer. Thus, other risk factors aside from H. pylori infection may be involved in gastric cancer development. This study aimed to investigate whether the nitrate-reducing bacteria isolated from patients with atrophic gastritis caused by H. pylori infection are risk factors for developing atrophic gastritis and gastric neoplasia. Nitrate-reducing bacteria were isolated from patients with atrophic gastritis caused by H. pylori infection. Among the isolated bacteria, Actinomyces oris, Actinomyces odontolyticus, Rothia dentocariosa, and Rothia mucilaginosa were used in the subsequent experiments. Cytokine inducibility was evaluated in monocytic cells, and mitogen-activated protein kinase (MAPK) activity and cell cycle were assessed in the gastric epithelial cells. The cytotoxicities and neutrophil-inducing abilities of the Actinomyces and Rothia species were enhanced when cocultured with H. pylori. Th1\/Th2-related cytokines were also expressed, but their expression levels differed depending on the bacterial species. Moreover, H. pylori and Actinomyces activated MAPK (ERK and p38) and affected cell cycle progression. Some nitrate-reducing bacteria cocultured with H. pylori may promote inflammation and atrophy by inducing cytokine production. In addition, the MAPK activation and cell cycle progression caused by these bacteria can contribute to gastric cancer development.<\/jats:p>","DOI":"10.3390\/microorganisms10122495","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T03:55:39Z","timestamp":1671162939000},"page":"2495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effects of Helicobacter pylori and Nitrate-Reducing Bacteria Coculture on Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Hinako","family":"Ojima","sequence":"first","affiliation":[{"name":"Department of Bacteriology, Academic Field of Health Sciences, Okayama University, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7038-9523","authenticated-orcid":false,"given":"Sakiko","family":"Kuraoka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyoutarou","family":"Okanoue","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Okada","sequence":"additional","affiliation":[{"name":"Himeji Red Cross Hospital, Himeji 670-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Gotoh","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Academic Field of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akari","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Oral Health Care and Rehabilitation, Institute of Biomedical Sciences, Graduate School, Tokushima University, Tokushima 770-0042, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Academic Field of Health Sciences, Okayama University, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/apt.14561","article-title":"Systematic review with meta-analysis: The worldwide prevalence of Helicobacter pylori infection","volume":"47","author":"Zamani","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_2","unstructured":"World Health Organization (1994). Infection with Helicobacter pylori. Schistosomes, Liver Flukes and Helicobacter pylori, IARC Mono-graphs."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1056\/NEJMoa001999","article-title":"Helicobacter pylori infection and the development of gastric cancer","volume":"345","author":"Uemura","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_4","first-page":"90","article-title":"Helicobacter pylori infection is the primary cause of gastric cancer","volume":"35","author":"Graham","year":"2000","journal-title":"J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S1470-2045(12)70137-7","article-title":"Global burden of cancers attributable to infections in 2008: A review and synthetic analysis","volume":"13","author":"Ferlay","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1128\/CMR.00011-10","article-title":"Helicobacter pylori and Gastric Cancer: Factors That Modulate Disease Risk","volume":"23","author":"Wroblewski","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1172\/JCI20925","article-title":"Helicobacter pylori persistence: Biology and disease","volume":"113","author":"Blaser","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1016\/j.jfma.2019.01.002","article-title":"Microbiota and gastrointestinal cancer","volume":"118","author":"Weng","year":"2019","journal-title":"J. Formos Med. Assoc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/hel.12145","article-title":"Differences in gastric mucosal microbiota profiling in patients with chronic gastritis, intestinal metaplasia, and gastric cancer using pyrosequencing methods","volume":"19","author":"Eun","year":"2014","journal-title":"Helicobacter"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1136\/gutjnl-2017-314281","article-title":"Mucosal microbiome dysbiosis in gastric carcinogenesis","volume":"67","author":"Coker","year":"2018","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1136\/gutjnl-2017-314205","article-title":"Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota","volume":"67","author":"Ferreira","year":"2018","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"505","DOI":"10.4161\/gmic.26205","article-title":"The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis","volume":"4","author":"Sheh","year":"2013","journal-title":"Gut Microbes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/35077232","article-title":"Genome maintenance mechanisms for preventing cancer","volume":"411","author":"Hoeijmakers","year":"2001","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1002\/jcp.30276","article-title":"Signaling, metabolism, and cancer: An important relationship for therapeutic intervention","volume":"236","author":"Ferns","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s12029-020-00518-5","article-title":"Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer","volume":"52","author":"Alipour","year":"2021","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.canlet.2013.08.016","article-title":"Helicobacter pylori-induced gastric inflammation and gastric cancer","volume":"45","author":"Wang","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_17","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5235","DOI":"10.3748\/wjg.v20.i18.5235","article-title":"Cytokines, cytokine gene polymorphisms and Helicobacter pylori infection: Friend or foe?","volume":"20","author":"Figueiredo","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1002\/jcp.25822","article-title":"Cytokine networks and their association with Helicobacter pylori infection in gastric carcinoma","volume":"233","author":"Bagheri","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wang, Z. (2021). Regulation of Cell Cycle Progression by Growth Factor-Induced Cell Signaling. 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Gastroenterol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/12\/2495\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:30Z","timestamp":1760146950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/12\/2495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,16]]},"references-count":22,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["microorganisms10122495"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms10122495","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,16]]}}}