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While intestinal FXR inhibition reduces high-fat diet (HFD)-induced hepatic steatosis, its role in MASH progression remains unclear. This study investigates the impact of intestinal FXR-deficiency on MASH development in a diet-induced murine model. Intestinal FXR-deficient (\n                    <jats:sup>int<\/jats:sup>\n                    FXR KO) and control mice were fed a high-fat, sucrose, and cholesterol-enriched diet (HFSC) for 24 weeks. Intestinal immune phenotyping, microarray, 16\u00a0S rRNA sequencing, bile acid quantification and liver assessments (histology, biochemistry and single-cell RNA sequencing (scRNA-seq)) were performed.\n                    <jats:sup>int<\/jats:sup>\n                    FXR KO mice were protected against HFSC diet-induced obesity and hepatic steatosis but exhibited altered expression of intestinal barrier-associated genes, with increased cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-lymphocytes. Microbiota composition and bile acid profiles were altered, including reduced Lachnospiraceae species correlating negatively with liver hyocholic acid levels. Despite a protection against hepatic steatosis, liver inflammation and fibrosis were unchanged in\n                    <jats:sup>int<\/jats:sup>\n                    FXR KO mice. Transcriptomic and Immune cell scRNA-seq analysis revealed alteration in immune-related pathways with an increased neutrophil proportion and higher cDC1:cDC2 and CD4:CD8 T cell ratios. Thus, intestinal FXR-deficiency limits steatosis but promote a distinct hepatic immune-inflammatory response and does not prevent progression to MASH.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-60976-y","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T14:13:43Z","timestamp":1783692823000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intestinal FXR deficiency uncouples steatosis protection from liver inflammation and fibrosis in MASH-diet fed mice"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4442-7180","authenticated-orcid":false,"given":"Margaux","family":"Nawrot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Peschard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane M","family":"Thibaut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e9vin","family":"Ory","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Vallez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Dorchies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Touche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Dubois-Chevalier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Gheeraert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Caron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadiombo","family":"Bantubungi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Lefebvre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Tailleux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel T","family":"Haas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure B","family":"Bindels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Leclercq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Dombrowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lestavel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Staels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"60976_CR1","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1016\/j.jhep.2023.06.003","volume":"79","author":"ME Rinella","year":"2023","unstructured":"Rinella, M. 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