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Background <p>This study aimed to investigate whether probiotics can ameliorate the <i>H. pylori</i>-induced Wnt/β-catenin-related COX-2 carcinogenesis signaling pathway by regulating the expression of microRNAs (miRNAs).</p> Methods <p>An <i>H. pylori</i> isolate and GES-1 cells were used to establish a COX-2-associated carcinogenesis axis. Western blot analysis was conducted to investigate Wnt/β-catenin and COX-2 signaling. Next-generation sequencing and DIANA Tools identified significant differences in miRNA expressions. The probiotics <i>Lactobacillus acidophilus</i> and <i>Bifidobacterium lactis</i> were used to study anti-carcinogenesis effects in GES-1 and miRNA-transfected GES-1 cells. The <i>H. pylori</i>-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.</p> Results <p>Pretreatment with probiotics significantly reduced <i>H. pylori</i>-induced nuclear β-catenin phosphorylation and COX-2 levels in GES-1 cells. Among 9 significantly altered miRNAs, miR-185 was the only miRNA targeting the Wnt/β-catenin signaling pathway. <i>H. pylori</i> increased miR-185 expression and upregulated COX-2 carcinogenesis through the Wnt/β-catenin pathway, but not the JAK2/STAT3 pathway. <i>B. lactis</i> ameliorated <i>H. pylori</i>-induced miR-185 expression and nuclear β-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: 1.134–18.65, <i>p</i> = 0.025; per-protocol: 46.2 vs 17.6%, OR: 4.00, 95% CI: 0.923–17.33, <i>p</i> = 0.055). Patients without IM regression had significantly higher miR-185 levels in follow-up biopsies (<i>p</i> &lt; 0.01).</p> Conclusions <p>Pretreatment with <i>B. lactis</i> ameliorated the <i>H. pylori</i>-induced COX-2 carcinogenesis pathway by reducing miR-185 expression, which targets Wnt/β-catenin signaling. (ClinicalTrials.gov, NCT05544396).</p>

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Probiotics ameliorate H. pylori-associated gastric β-catenin and COX-2 carcinogenesis signaling by regulating miR-185

  • 期刊论文

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  • 发表日期：

    2025年6月3日

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  • Yao-Jong Yang,
  • Chung-Tai Wu,
  • Hsiu-Chi Cheng,
  • Wei-Ying Chen,
  • Joseph T. Tseng,
  • Wei-Lun Chang,
  • Bor-Shyang Sheu

摘要

Background

This study aimed to investigate whether probiotics can ameliorate the H. pylori-induced Wnt/β-catenin-related COX-2 carcinogenesis signaling pathway by regulating the expression of microRNAs (miRNAs).

Methods

An H. pylori isolate and GES-1 cells were used to establish a COX-2-associated carcinogenesis axis. Western blot analysis was conducted to investigate Wnt/β-catenin and COX-2 signaling. Next-generation sequencing and DIANA Tools identified significant differences in miRNA expressions. The probiotics Lactobacillus acidophilus and Bifidobacterium lactis were used to study anti-carcinogenesis effects in GES-1 and miRNA-transfected GES-1 cells. The H. pylori-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.

Results

Pretreatment with probiotics significantly reduced H. pylori-induced nuclear β-catenin phosphorylation and COX-2 levels in GES-1 cells. Among 9 significantly altered miRNAs, miR-185 was the only miRNA targeting the Wnt/β-catenin signaling pathway. H. pylori increased miR-185 expression and upregulated COX-2 carcinogenesis through the Wnt/β-catenin pathway, but not the JAK2/STAT3 pathway. B. lactis ameliorated H. pylori-induced miR-185 expression and nuclear β-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: 1.134–18.65, p = 0.025; per-protocol: 46.2 vs 17.6%, OR: 4.00, 95% CI: 0.923–17.33, p = 0.055). Patients without IM regression had significantly higher miR-185 levels in follow-up biopsies (p < 0.01).

Conclusions

Pretreatment with B. lactis ameliorated the H. pylori-induced COX-2 carcinogenesis pathway by reducing miR-185 expression, which targets Wnt/β-catenin signaling. (ClinicalTrials.gov, NCT05544396).