Spatial Variation of the Gastrointestinal Microbiota in Response to Long-Term Administration of Vonoprazan in Mice With High Risk of Gastric Cancer

IF 4.3 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter Pub Date : 2024-07-31 DOI:10.1111/hel.13117

Chao Peng, Xinbo Xu, Yaobin Ouyang, Yu Li, Nonghua Lu, Yin Zhu, Cong He

{"title":"Spatial Variation of the Gastrointestinal Microbiota in Response to Long-Term Administration of Vonoprazan in Mice With High Risk of Gastric Cancer","authors":"Chao Peng, Xinbo Xu, Yaobin Ouyang, Yu Li, Nonghua Lu, Yin Zhu, Cong He","doi":"10.1111/hel.13117","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Vonoprazan, a potassium-competitive acid blocker, is superior to traditional proton pump inhibitor (PPI) in acid suppression and has been approved in the treatment of acid-related disorders. Accumulating evidence suggest associations between PPI use and gut microbiota, yet the effect of vonoprazan on GI microbiota is obscure.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer (GC) were administered vonoprazan by gavage every other day for 12 weeks. Stomachs were evaluated by histopathology, Ki-67 proliferation index, and inflammatory cytokines. The mucosal and lumen microbiota from stomach, jejunum, ileum, cecum, and feces were detected using 16S rRNA gene sequencing.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Higher incidence of intestinal metaplasia and epithelial proliferation were observed in the vonoprazan group than that in the control mice. Vonoprazan also elevated the gastric expression of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6. Each mice comprised a unique microbiota composition that was consistent across different niches. The structure of GI microbiota changed dramatically after vonoprazan treatment with the stomach being the most disturbed segment. Vonoprazan administration shifted the gut microbiota toward the enrichment of pathogenic <i>Streptococcus</i>, <i>Staphylococcus</i>, <i>Bilophila</i>, and the loss of commensal <i>Prevotella</i>, <i>Bifidobacterium</i>, and <i>Faecalibacterium</i>. Interestingly, compared to the controls, microbial interactions were weaker in the stomach while stronger in the jejunum of the vonoprazan group.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Long-term vonoprazan treatment promoted gastric lesions in male INS-GAS mice, with the disequilibrium of GI microbiome. The clinical application of vonoprazan needs to be judicious particularly among those with high risk of GC.</p>\n </section>\n </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"29 4","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Helicobacter","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/hel.13117","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Vonoprazan, a potassium-competitive acid blocker, is superior to traditional proton pump inhibitor (PPI) in acid suppression and has been approved in the treatment of acid-related disorders. Accumulating evidence suggest associations between PPI use and gut microbiota, yet the effect of vonoprazan on GI microbiota is obscure.

Methods

Transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer (GC) were administered vonoprazan by gavage every other day for 12 weeks. Stomachs were evaluated by histopathology, Ki-67 proliferation index, and inflammatory cytokines. The mucosal and lumen microbiota from stomach, jejunum, ileum, cecum, and feces were detected using 16S rRNA gene sequencing.

Results

Higher incidence of intestinal metaplasia and epithelial proliferation were observed in the vonoprazan group than that in the control mice. Vonoprazan also elevated the gastric expression of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6. Each mice comprised a unique microbiota composition that was consistent across different niches. The structure of GI microbiota changed dramatically after vonoprazan treatment with the stomach being the most disturbed segment. Vonoprazan administration shifted the gut microbiota toward the enrichment of pathogenic Streptococcus, Staphylococcus, Bilophila, and the loss of commensal Prevotella, Bifidobacterium, and Faecalibacterium. Interestingly, compared to the controls, microbial interactions were weaker in the stomach while stronger in the jejunum of the vonoprazan group.

Conclusions

Long-term vonoprazan treatment promoted gastric lesions in male INS-GAS mice, with the disequilibrium of GI microbiome. The clinical application of vonoprazan needs to be judicious particularly among those with high risk of GC.

查看原文本刊更多论文

胃癌高风险小鼠长期服用沃诺普拉赞后胃肠道微生物群的空间变化

背景：Vonoprazan是一种钾竞争性酸阻滞剂，在抑酸方面优于传统的质子泵抑制剂（PPI），已被批准用于治疗酸相关疾病。越来越多的证据表明，PPI的使用与肠道微生物群之间存在关联，但vonoprazan对消化道微生物群的影响尚不明确：方法：以转基因 FVB/N 胰岛素-胃泌素（INS-GAS）小鼠为胃癌（GC）模型，每隔一天灌胃一次 vonoprazan，持续 12 周。通过组织病理学、Ki-67 增殖指数和炎症细胞因子对胃进行评估。用 16S rRNA 基因测序法检测了胃、空肠、回肠、盲肠和粪便的粘膜和腔内微生物群：结果：与对照组小鼠相比，Vonoprazan 组小鼠的肠化生和上皮增生发生率更高。此外，Vonoprazan 还提高了胃中促炎细胞因子的表达，包括 TNF-α、IL-1β 和 IL-6。每只小鼠都有独特的微生物群组成，这些组成在不同的龛位中是一致的。沃诺普拉赞治疗后，胃肠道微生物群的结构发生了显著变化，其中胃部受到的干扰最大。服用沃诺普拉赞后，肠道微生物群中致病性链球菌、葡萄球菌和嗜双球菌增多，而共生的普雷沃特氏菌、双歧杆菌和粪杆菌则减少。有趣的是，与对照组相比，vonoprazan 组胃部微生物相互作用较弱，而空肠微生物相互作用较强：结论：vonoprazan的长期治疗促进了雄性INS-GAS小鼠的胃部病变，并导致消化道微生物组的失衡。临床应用沃诺普拉赞需要慎重，尤其是在胃癌高危人群中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Helicobacter 医学-微生物学

CiteScore

8.40

自引率

9.10%

发文量

审稿时长

2 months

期刊介绍： Helicobacter is edited by Professor David Y Graham. The editorial and peer review process is an independent process. Whenever there is a conflict of interest, the editor and editorial board will declare their interests and affiliations. Helicobacter recognises the critical role that has been established for Helicobacter pylori in peptic ulcer, gastric adenocarcinoma, and primary gastric lymphoma. As new helicobacter species are now regularly being discovered, Helicobacter covers the entire range of helicobacter research, increasing communication among the fields of gastroenterology; microbiology; vaccine development; laboratory animal science.