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Herein, the influences of different GAIs on NSAID\u2010induced intestinal injury and the underlying mechanisms are clarified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Indomethacin (IND; 10\u00a0mg\/kg\/day) was administered to mice to induce small intestinal injury. Disease activity was examined macroscopically and histologically. The permeability of small intestine was evaluated by measuring plasma lipopolysaccharide levels. 16S rDNA sequencing was performed to determine the composition of intestinal flora.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the four GAIs, ilaprazole (IPZ) significantly attenuated IND\u2010induced small intestinal injury and maintained the integrity of the mucosal barrier. Omeprazole (OPZ) and vonoprazan (VPZ) ameliorated ulceration without significant differences, while rabeprazole (RPZ) failed to protect against the injury. To explore the potential mechanism, we investigated changes in the gut microbiota mediated by GAIs. After 5\u2010day administration, GAIs significantly altered the composition of the gut microbiota. The IND group had a significant decrease in alpha diversity compared with the control group, and this decrease was reversed by OPZ and IPZ treatment, respectively. After IPZ treatment, the community membership was more assembled in the control group than the IND group. Further, we found that <jats:italic>Lactobacillus<\/jats:italic> was significantly increased in the groups of OPZ, IPZ, and VPZ, while <jats:italic>Bacteroides<\/jats:italic> was significantly increased in the RPZ group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicated that GAIs have different influences on the mucosal barrier, possibly by altering the composition of intestinal microbiota, and the impacts mediated by various GAIs in the IND\u2010induced intestinal damage model seem different.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.15973","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T12:06:13Z","timestamp":1659960373000},"page":"1935-1945","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The influence of different proton pump inhibitors and potassium\u2010competitive acid blockers on indomethacin\u2010induced small intestinal injury"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0996-1804","authenticated-orcid":false,"given":"Kemin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"},{"name":"Key Laboratory of Gut Microbiota Translational Medicine Research Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"},{"name":"Key Laboratory of Gut Microbiota Translational Medicine Research Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taotao","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"},{"name":"Key Laboratory of Gut Microbiota Translational Medicine Research Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9292-9225","authenticated-orcid":false,"given":"Jingnan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"},{"name":"Key Laboratory of Gut Microbiota Translational Medicine Research Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91843-0"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712803414105"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12858"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.164"},{"key":"e_1_2_5_6_1","first-page":"89","article-title":"Lansoprazole, a proton pump inhibitor, reduces the severity of indomethacin\u2010induced rat enteritis","volume":"17","author":"Kuroda M","year":"2006","journal-title":"Int. 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