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Probiotics have been shown to attenuate <jats:italic>H. pylori<\/jats:italic>\u2010induced gastritis, although their role in cancer prevention remains unclear. Thus, we aimed to explore the effects of probiotics on <jats:italic>H. pylori<\/jats:italic>\u2010induced carcinogenesis and the alterations of gastrointestinal microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male INS\u2010GAS mice were randomly allocated to <jats:italic>H. pylori<\/jats:italic>\u2010infected and non\u2010infected groups. After 4\u2009weeks, probiotic combination (containing <jats:italic>Lactobacillus salivarius<\/jats:italic> and <jats:italic>Lactobacillus rhamnosus<\/jats:italic>) was administered in drinking water for 12\u2009weeks. Stomachs were collected for RNA\u2010Sequencing and the differentially expressed genes were validated using RT profiler PCR array. 16S rRNA gene sequencing was performed to assess the alterations of gastrointestinal microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Probiotics significantly alleviate <jats:italic>H. pylori<\/jats:italic>\u2010induced gastric pathology, including reduced infiltration of inflammation and lower incidence of precancerous lesions. RNA\u2010Sequencing results showed that probiotics treatment decreased expressions of genes involved in pro\u2010inflammatory pathways, such as NF\u2010\u03baB, IL\u201017, and TNF signaling pathway. Of note, probiotics did not suppress the growth of <jats:italic>H. pylori<\/jats:italic>, but dramatically reshaped the structure of both gastric and gut microbiota. The microbial diversity was increased in <jats:italic>H. pylori<\/jats:italic>\u2010infected group after probiotics treatment. While gastric cancer\u2010associated genera <jats:italic>Lactobacillus<\/jats:italic> and <jats:italic>Staphylococcus<\/jats:italic> were enriched in the stomach of <jats:italic>H. pylori<\/jats:italic>\u2010infected group, the beneficial short\u2010chain fatty acids\u2010producing bacteria, including <jats:italic>Bacteroides<\/jats:italic>, <jats:italic>Alloprevotella<\/jats:italic>, and <jats:italic>Oscellibacter<\/jats:italic>, were more abundant in mice treated with probiotics. Additionally, probiotics restored the <jats:italic>H. pylori<\/jats:italic>\u2010induced reduction of anti\u2010inflammatory bacterium <jats:italic>Faecalibaculum<\/jats:italic> in the gut.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Probiotics therapy can protect against <jats:italic>H. pylori<\/jats:italic>\u2010associated carcinogenesis probably through remodeling gastrointestinal microbiota, which in turn prevent host cells from malignant transformation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.12898","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T07:54:53Z","timestamp":1652082893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Probiotics mitigate Helicobacter pylori\u2010induced gastric inflammation and premalignant lesions in INS\u2010GAS mice with the modulation of gastrointestinal microbiota"],"prefix":"10.1111","volume":"27","author":[{"given":"Cong","family":"He","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-3904","authenticated-orcid":false,"given":"Chao","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinbo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianshuang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Nanchang University  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