{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T03:51:34Z","timestamp":1777002694063,"version":"3.51.4"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"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":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>To analyze the effects of fexaramine (FEX), as an intestinal FXR agonist, on the modulation of the intestinal microbiota and ileum of mice fed a high\u2010fat (HF) diet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Three\u2010month\u2010old C57Bl\/6 male mice are divided into two groups and received a control (C, 10% of energy from lipids) or HF (50% of energy from lipids) diet for 12 weeks. They are subdivided into the C, C\u00a0+\u00a0FEX, HF, and HF\u00a0+\u00a0FEX groups. FEX is administered (FEX\u20105\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>) via orogastric gavage for three weeks. Body mass (BM), glucose metabolism, qPCR\u00a016S\u00a0rRNA gene expression, and ileum gene expression, bile acids (BAs), tight junctions (TJs), and incretin are analyzed. FEX reduces BM and glucose intolerance, reduces plasma lipid concentrations and the <jats:italic>Firmicutes<\/jats:italic>\/<jats:italic>Bacteroidetes<\/jats:italic> ratio, increases the <jats:italic>Lactobacillus<\/jats:italic> sp. and <jats:italic>Prevotella<\/jats:italic> sp. abundance, and reduces the <jats:italic>Escherichia coli<\/jats:italic> abundance. Consequently, the ileal gene expression of <jats:italic>Fxr\u2010Fgf15<\/jats:italic>, <jats:italic>Tgr5\u2010Glp1<\/jats:italic>, and <jats:italic>Cldn\u2010Ocldn\u2010Zo1<\/jats:italic> is increased, and <jats:italic>Tlr4\u2010Il6\u2010Il1beta<\/jats:italic> is decreased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>FEX stimulates intestinal FXR and improves dysbiosis, intestinal TJs, and the release of incretins, mitigating glucose intolerance and BM increases induced by an HF diet. However, FEX results in glucose intolerance, insulin resistance, and reduces intestinal TJs in a control group, thus demonstrating limitations to this dietary model.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202300148","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:29:24Z","timestamp":1702427364000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["An Intestinal FXR Agonist Mitigates Dysbiosis, Intestinal Tight Junctions, and Inflammation in High\u2010Fat Diet\u2010Fed Mice"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7417-7448","authenticated-orcid":false,"given":"Tamiris Ingrid","family":"Petito\u2010da\u2010Silva","sequence":"first","affiliation":[{"name":"Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology The University of the State of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5536-7526","authenticated-orcid":false,"suffix":"J\u00fanior","given":"Felipe Missiba","family":"Villardi","sequence":"additional","affiliation":[{"name":"Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology The University of the State of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9595-9852","authenticated-orcid":false,"given":"Aline","family":"Penna\u2010de\u2010Carvalho","sequence":"additional","affiliation":[{"name":"Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology The University of the State of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4134-7978","authenticated-orcid":false,"given":"Carlos Alberto","family":"Mandarim\u2010de\u2010Lacerda","sequence":"additional","affiliation":[{"name":"Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology The University of the State of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2510-9569","authenticated-orcid":false,"given":"Vanessa","family":"Souza\u2010Mello","sequence":"additional","affiliation":[{"name":"Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology The University of the State of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3866-0912","authenticated-orcid":false,"given":"Sandra","family":"Barbosa\u2010da\u2010Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology The University of the State of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.54"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00027-19"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12010056"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abp9960"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2022.111618"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.906452"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-324305"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23116046"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-019-10001-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.08.057"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3760"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2019_233"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29857"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/123.11.1939"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.11005\/jbm.2017.24.4.207"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2007.05.009"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v28.i17.1814"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2019.110539"},{"key":"e_1_2_9_19_1","first-page":"1723","volume":"42","author":"Liu Y.","year":"2018","journal-title":"Int. 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