{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:40:50Z","timestamp":1790775650598,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"INCT Obesidade e Diabetes CNPq","award":["465693\/2014-8"],"award-info":[{"award-number":["465693\/2014-8"]}]},{"name":"INCT Obesidade e Diabetes CNPq","award":["2014\/50907-5"],"award-info":[{"award-number":["2014\/50907-5"]}]},{"name":"INCT Obesidade e Diabetes CNPq","award":["2019\/03196-0"],"award-info":[{"award-number":["2019\/03196-0"]}]},{"name":"INCT Obesidade e Diabetes CNPq","award":["2020\/06397-3"],"award-info":[{"award-number":["2020\/06397-3"]}]},{"name":"FAPESP","award":["465693\/2014-8"],"award-info":[{"award-number":["465693\/2014-8"]}]},{"name":"FAPESP","award":["2014\/50907-5"],"award-info":[{"award-number":["2014\/50907-5"]}]},{"name":"FAPESP","award":["2019\/03196-0"],"award-info":[{"award-number":["2019\/03196-0"]}]},{"name":"FAPESP","award":["2020\/06397-3"],"award-info":[{"award-number":["2020\/06397-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or weight gain, it is an interesting model to correlate microbiota modulation with the establishment of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of pantoprazole treatment on TLR4 signaling and liver histology in C57BL\/6J mice for 60 days, trying to correlate microbiota modulation with some aspects of liver injury. We performed glucose (GTT) and insulin (ITT) tolerance tests, serum lipopolysaccharide (LPS) dosage, liver histology, liver and intestine extraction for Western blot and qPCR. Fecal microbiota were investigated via metagenomics. Chronic treatment with pantoprazole induced microbiota modulation and impaired ileum barrier integrity, without an association with insulin resistance. Furthermore, increased circulating LPS and increased Toll-like receptor 4 (TLR4) and TGF\u03b2 downstream signaling may have an important role in the development of the observed liver microvesicular steatosis and fibrosis. Finally, this model of PPI-induced changes in microbiota might be useful to investigate liver microvesicular steatosis and fibrosis.<\/jats:p>","DOI":"10.3390\/ijms232213766","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T01:48:08Z","timestamp":1668044888000},"page":"13766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1269-9624","authenticated-orcid":false,"given":"Heloisa B.","family":"Assalin","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly Cristiane Gabriel","family":"De Almeida","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dioze","family":"Guadagnini","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-1130","authenticated-orcid":false,"given":"Caio J.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0192-8869","authenticated-orcid":false,"given":"Silvana","family":"Bordin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7403-3230","authenticated-orcid":false,"given":"Guilherme Z.","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario J. A.","family":"Saad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1159\/000091298","article-title":"Acid suppression therapy: Where do we go from here?","volume":"24","author":"Scarpignato","year":"2006","journal-title":"Dig. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/j.1572-0241.2005.41217.x","article-title":"Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease","volume":"100","author":"DeVault","year":"2005","journal-title":"Am. J. 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