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Western blot analysis was conducted to investigate Wnt\/\u03b2-catenin and COX-2 signaling. Next-generation sequencing and DIANA Tools identified significant differences in miRNA expressions. The probiotics <jats:italic>Lactobacillus acidophilus<\/jats:italic> and <jats:italic>Bifidobacterium lactis<\/jats:italic> were used to study anti-carcinogenesis effects in GES-1 and miRNA-transfected GES-1 cells. The <jats:italic>H. pylori<\/jats:italic>-infected patients with intestinal metaplasia (IM) were randomly allocated into probiotic treatment or not after successful eradication, the IM regression was assessed by the 2nd esophagogastroduodenoscopy one year after treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Pretreatment with probiotics significantly reduced <jats:italic>H. pylori<\/jats:italic>-induced nuclear \u03b2-catenin phosphorylation and COX-2 levels in GES-1 cells. Among 9 significantly altered miRNAs, miR-185 was the only miRNA targeting the Wnt\/\u03b2-catenin signaling pathway. <jats:italic>H. pylori<\/jats:italic> increased miR-185 expression and upregulated COX-2 carcinogenesis through the Wnt\/\u03b2-catenin pathway, but not the JAK2\/STAT3 pathway. <jats:italic>B. lactis<\/jats:italic> ameliorated <jats:italic>H. pylori<\/jats:italic>-induced miR-185 expression and nuclear \u03b2-catenin\/COX-2 signaling in a dose-dependent manner. In the 6-month probiotic-treated patients had a significantly higher IM regression rate than controls (intention-to-treat: 37.5 vs 11.5%, OR: 4.60, 95% CI: 1.134\u201318.65, <jats:italic>p<\/jats:italic>\u2009=\u20090.025; per-protocol: 46.2 vs 17.6%, OR: 4.00, 95% CI: 0.923\u201317.33, <jats:italic>p<\/jats:italic>\u2009=\u20090.055). Patients without IM regression had significantly higher miR-185 levels in follow-up biopsies (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Pretreatment with <jats:italic>B. lactis<\/jats:italic> ameliorated the <jats:italic>H. pylori<\/jats:italic>-induced COX-2 carcinogenesis pathway by reducing miR-185 expression, which targets Wnt\/\u03b2-catenin signaling. (ClinicalTrials.gov, NCT05544396).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12929-025-01149-3","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T06:35:10Z","timestamp":1748932510000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Probiotics ameliorate H. pylori-associated gastric \u03b2-catenin and COX-2 carcinogenesis signaling by regulating miR-185"],"prefix":"10.1186","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2164-138X","authenticated-orcid":false,"given":"Yao-Jong","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Tai","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu-Chi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph T.","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Lun","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bor-Shyang","family":"Sheu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"issue":"11","key":"1149_CR1","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1056\/NEJMoa001999","volume":"345","author":"N Uemura","year":"2001","unstructured":"Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. 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(A-BR-106-085).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Name: Study on the Probiotics Regulating miRNA in H. pylori-induced Wnt\/\u03b2-catenin Gastric Carcinogenesis. ClinicalTrials.gov ID: NCT05544396. Date of registered this trial: March 20, 2024. .","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"The name of Randomized Clinical Trials registry and the registration number"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"55"}}