{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:46:29Z","timestamp":1785415589712,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,10]]},"group-title":"Microbiology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R00CA263036"],"award-info":[{"award-number":["R00CA263036"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30CA023168"],"award-info":[{"award-number":["P30CA023168"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001368","name":"V Foundation for Cancer Research","doi-asserted-by":"crossref","award":["V2025-030"],"award-info":[{"award-number":["V2025-030"]}],"id":[{"id":"10.13039\/100001368","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001377","name":"Walther Cancer Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001377","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Stomach infection with the bacterium\n                  <jats:italic>Helicobacter pylori<\/jats:italic>\n                  (\n                  <jats:italic>Hp<\/jats:italic>\n                  ) can cause chronic gastric inflammation, metaplasia (transdifferentiation of mature cell types), dysplasia (abnormal cells), and finally cancer. Obesity can also increase gastric cancer risk. However, host-\n                  <jats:italic>Hp<\/jats:italic>\n                  interactions during obesity are poorly understood. Here we investigated the impact of diet-induced obesity in two mouse models of\n                  <jats:italic>Hp<\/jats:italic>\n                  -associated disease. To model chronic gastric inflammation, we used C57BL\/6 mice, and to model more severe disease, we used transgenic mice in which tamoxifen induces gastric expression of a constitutively active\n                  <jats:italic>Kras<\/jats:italic>\n                  allele, leading to metaplasia. We fed mice a high-fat diet (60% kilocalories from fat) to induce obesity, or a matched control diet (10% kilocalories from fat), then infected them with\n                  <jats:italic>Hp<\/jats:italic>\n                  or mock-infected them. In mock-infected C57BL\/6 mice, high-fat diet had a minimal impact on gastric pathology and gene expression. In\n                  <jats:italic>Hp<\/jats:italic>\n                  -infected C57BL\/6 mice, high-fat diet increased inflammation at the junction between the glandular stomach and non-glandular forestomach, a squamous epithelium similar to the human esophagus, and increased gastric expression of the cancer-associated genes\n                  <jats:italic>Cldn7<\/jats:italic>\n                  and\n                  <jats:italic>Reg3g<\/jats:italic>\n                  . In KRAS+ mice with or without\n                  <jats:italic>Hp<\/jats:italic>\n                  infection, the impact of diet-induced obesity was more apparent, with increased metaplasia and dysplasia (abnormal cells). As well, high-fat diet caused an expansion of metaplastic pit cells, a lineage we previously found to be associated with\n                  <jats:italic>Hp<\/jats:italic>\n                  -driven inflammation. Thus, in these mouse models, diet-induced obesity does not directly drive gastric immunopathology, but enhances the development of pre-cancerous changes under susceptible conditions.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>\n                    Most gastric cancers are caused by stomach infection with the bacterium\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    . However, most infected individuals never develop cancer. Therefore, additional risk factors must tip the balance toward gastric cancer development. Obesity, or excessive body fat accumulation that poses a risk to health, is associated with gastric cancer development. However, specific mechanisms for obesity-driven gastric cancer risk are not well defined. Here we tested the hypothesis that obesity would exacerbate\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    -associated disease phenotypes using two clinically relevant mouse models. In wild-type mice, obesity induced by a very high-fat diet had a minimal impact on the stomach in the absence of infection, but increased the expression of some cancer-associated genes during infection. However, in mice with genetically driven pre-cancer, diet-induced obesity exacerbated the disease pathology, especially in infected mice. Therefore, obesity\u2019s impact on gastric cancer risk may be more evident in the later stages of the disease.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.10.737708","type":"posted-content","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T11:35:31Z","timestamp":1783769731000},"source":"Crossref","is-referenced-by-count":0,"title":["Diet-Induced Obesity Exacerbates\n                  <i>Helicobacter pylori<\/i>\n                  -Associated Precancerous Phenotypes"],"prefix":"10.64898","author":[{"given":"Xuyao","family":"Zhao","sequence":"first","affiliation":[{"name":"Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Nicholas","family":"Wojcicki","sequence":"additional","affiliation":[{"name":"Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kee-Hong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Food Science, Purdue University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia Atallah","family":"Lanman","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology, Purdue University"},{"name":"Purdue Institute for Cancer Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viju","family":"Vijayan Pillai","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology, Purdue University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-2690","authenticated-orcid":false,"given":"Valerie Phoebe","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University"},{"name":"Purdue Institute for Cancer Research"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071411001009000_2026.07.10.737708v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30488-7"},{"key":"2026071411001009000_2026.07.10.737708v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020542"},{"key":"2026071411001009000_2026.07.10.737708v1.3","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.09.005"},{"issue":"13","key":"2026071411001009000_2026.07.10.737708v1.4","first-page":"3554","article-title":"A human model of gastric carcinogenesis","volume":"48","year":"1988","journal-title":"Cancer Res"},{"key":"2026071411001009000_2026.07.10.737708v1.5","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.04.023"},{"key":"2026071411001009000_2026.07.10.737708v1.6","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00054-05"},{"key":"2026071411001009000_2026.07.10.737708v1.7","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100328"},{"key":"2026071411001009000_2026.07.10.737708v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(75)90498-5"},{"key":"2026071411001009000_2026.07.10.737708v1.9","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.02.007"},{"key":"2026071411001009000_2026.07.10.737708v1.10","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.02.077"},{"key":"2026071411001009000_2026.07.10.737708v1.11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.12.6977"},{"key":"2026071411001009000_2026.07.10.737708v1.12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803293"},{"key":"2026071411001009000_2026.07.10.737708v1.13","doi-asserted-by":"crossref","unstructured":"Emmerich SD FC , Stierman B , Ogden CL . Obesity and severe obesity prevalence in adults: United States, August 2021\u2013August 2023. NCHS Data Brief [Internet]. 2024 9\/21\/2025; 508. Available from: https:\/\/www.cdc.gov\/nchs\/products\/databriefs\/db508","DOI":"10.15620\/cdc\/159281"},{"key":"2026071411001009000_2026.07.10.737708v1.14","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012615-044359"},{"key":"2026071411001009000_2026.07.10.737708v1.15","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-18-0733"},{"key":"2026071411001009000_2026.07.10.737708v1.16","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-014-0429-0"},{"key":"2026071411001009000_2026.07.10.737708v1.17","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2021.130"},{"key":"2026071411001009000_2026.07.10.737708v1.18","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.11.726"},{"key":"2026071411001009000_2026.07.10.737708v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3808"},{"key":"2026071411001009000_2026.07.10.737708v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2009.04.019"},{"key":"2026071411001009000_2026.07.10.737708v1.21","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.2.150"},{"key":"2026071411001009000_2026.07.10.737708v1.22","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202000967"},{"key":"2026071411001009000_2026.07.10.737708v1.23","doi-asserted-by":"publisher","DOI":"10.1158\/2767-9764.CRC-23-0142"},{"key":"2026071411001009000_2026.07.10.737708v1.24","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03116-22"},{"key":"2026071411001009000_2026.07.10.737708v1.25","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.116665"},{"key":"2026071411001009000_2026.07.10.737708v1.26","doi-asserted-by":"publisher","DOI":"10.3945\/an.114.006940"},{"key":"2026071411001009000_2026.07.10.737708v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2013.11.022"},{"issue":"2","key":"2026071411001009000_2026.07.10.737708v1.28","first-page":"377","article-title":"Up-regulated claudin 7 expression in intestinal-type gastric carcinoma","volume":"18","year":"2007","journal-title":"Oncol Rep"},{"key":"2026071411001009000_2026.07.10.737708v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01054-5"},{"key":"2026071411001009000_2026.07.10.737708v1.30","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.11.049"},{"key":"2026071411001009000_2026.07.10.737708v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.10.003"},{"key":"2026071411001009000_2026.07.10.737708v1.32","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01867-14"},{"key":"2026071411001009000_2026.07.10.737708v1.33","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018897922644"},{"key":"2026071411001009000_2026.07.10.737708v1.34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.54.1.615"},{"key":"2026071411001009000_2026.07.10.737708v1.35","doi-asserted-by":"publisher","DOI":"10.5114\/pg.2018.80001"},{"key":"2026071411001009000_2026.07.10.737708v1.36","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-07-0704"},{"key":"2026071411001009000_2026.07.10.737708v1.37","doi-asserted-by":"publisher","DOI":"10.1097\/CEJ.0b013e3282f521e4"},{"key":"2026071411001009000_2026.07.10.737708v1.38","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-13-0042"},{"key":"2026071411001009000_2026.07.10.737708v1.39","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12946"},{"key":"2026071411001009000_2026.07.10.737708v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.gie.2019.07.038"},{"key":"2026071411001009000_2026.07.10.737708v1.41","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00015-24"},{"key":"2026071411001009000_2026.07.10.737708v1.42","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305092"},{"key":"2026071411001009000_2026.07.10.737708v1.43","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.10.025"},{"key":"2026071411001009000_2026.07.10.737708v1.44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030786"},{"key":"2026071411001009000_2026.07.10.737708v1.45","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.06.047"},{"key":"2026071411001009000_2026.07.10.737708v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/J.ABB.2016.09.015"},{"key":"2026071411001009000_2026.07.10.737708v1.47","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-016-0066-1"},{"key":"2026071411001009000_2026.07.10.737708v1.48","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-005-2_22"},{"key":"2026071411001009000_2026.07.10.737708v1.49","doi-asserted-by":"publisher","DOI":"10.14670\/HH-18-503"},{"key":"2026071411001009000_2026.07.10.737708v1.50","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2012.657"},{"key":"2026071411001009000_2026.07.10.737708v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-019-0363-7"},{"key":"2026071411001009000_2026.07.10.737708v1.52","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"2026071411001009000_2026.07.10.737708v1.53","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2026071411001009000_2026.07.10.737708v1.54","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2026071411001009000_2026.07.10.737708v1.55","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf018"},{"key":"2026071411001009000_2026.07.10.737708v1.56","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.10.737708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:00:19Z","timestamp":1784052019000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.07.10.737708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":56,"URL":"https:\/\/doi.org\/10.64898\/2026.07.10.737708","relation":{},"subject":[],"published":{"date-parts":[[2026,7,10]]},"subtype":"preprint"}}