{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:43:08Z","timestamp":1790775788649,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T00:00:00Z","timestamp":1587427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intestinal permeability and psychological stress are considered the key mechanism(s) in functional dyspepsia (FD). Although proton pump inhibitors (PPIs) are commonly used for the treatment of FD, the effect of PPIs on intestinal permeability has not been elucidated. This study investigated the effect of PPI on intestinal permeability under stressed conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57BL\/6J mice were subjected to water avoidance stress (WAS) and administered rabeprazole (40\u00a0mg\/kg) or vehicle treatment (VT). We then evaluated intestinal permeability both in vivo and ex vivo using plasma fluorescein isothiocyanate\u2010dextran and by assessing the paracellular permeability and transepithelial electrical resistance (TEER) in an Ussing chamber, respectively. Furthermore, we evaluated the effect of PPI\u2010treated fecal microbiota transplant (FMT) on intestinal permeability in vivo. Microbiota profiles of donor feces were assessed by 16S rRNA gene analysis using MiSeq and QIIME2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In the WAS treatment, PPI significantly enhanced intestinal permeability in vivo compared to that in VT. Moreover, PPI significantly increased paracellular permeability and decreased TEER in the duodenum and jejunum, respectively, compared to those in VT under stressed conditions. Moreover, both vasoactive intestinal peptide (VIP) receptor antagonist and ketotifen significantly reversed the effect of PPI on intestinal permeability. Furthermore, PPI\u2010treated FMT significantly increased the intestinal permeability in vivo compared to that in vehicle\u2010treated FMT. Proton pump inhibitors treatment altered the gut microbiota composition, indicating that PPI induced dysbiosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>Under stressed conditions, PPI enhances intestinal permeability via dysbiosis of gut microbiota. Vasoactive intestinal peptide and mast cells are also implicated in the underlying mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13841","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T02:20:29Z","timestamp":1587522029000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice"],"prefix":"10.1111","volume":"32","author":[{"given":"Shingo","family":"Takashima","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9186-1249","authenticated-orcid":false,"given":"Fumio","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunosuke","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Immunology and Genomics Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Usui","sequence":"additional","affiliation":[{"name":"Division of Systems Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Immunology and Genomics Osaka City University Graduate School of Medicine Osaka Japan"},{"name":"Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines The Institute of Medical Science The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Nadatani","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Otani","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Hosomi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuaki","family":"Nagami","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Kamata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Taira","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Tanigawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiya","family":"Imoto","sequence":"additional","affiliation":[{"name":"Division of Health Medical Data Science Health Intelligence Center The Institute of Medical Science The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Uematsu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Genomics Osaka City University Graduate School of Medicine Osaka Japan"},{"name":"Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines The Institute of Medical Science The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-006-0011-4"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303857"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-016-4329-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.085373"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305690"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12127"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00066.2003"},{"issue":"2","key":"e_1_2_9_9_1","first-page":"R362","article-title":"VIP, serotonin, and epinephrine modulate the ion selectivity of tight junctions of goldfish intestine","volume":"264","author":"Bakker R","year":"1993","journal-title":"Am J Physiol"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90551.2008"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.154"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-014-1022-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.06.075"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i22.2706"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-016-1205-1"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03824.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12154"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.22470"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2008.09.016"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.618249"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09922"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar\/ilv010"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.002"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxy035"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep46037"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.244"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.02.038"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.06.051"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ctg.2015.20"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.06.043"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134234"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00460-18"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.080739"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2000.00025.x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00327.2009"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.13841","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nmo.13841","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.13841","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T10:36:13Z","timestamp":1693910173000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.13841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,21]]},"references-count":34,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/nmo.13841"],"URL":"https:\/\/doi.org\/10.1111\/nmo.13841","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,21]]},"assertion":[{"value":"2019-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13841"}}