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Obesity and insulin resistance are associated with GM dysbiosis. The GM is strongly associated with metabolic disorders and fatty liver disease. The co-chaperone protein FK506-binding protein-5 (FKBP5) regulates several vital cellular processes. Although FKBP5 has been implicated in stress-related disorders, it has not been directly linked to HFD-induced metabolic fatty liver disease. This study aimed to elucidate how FK506 binding protein 5 impairment affects the GM in HFD-induced metabolic dysfunction\u2013associated fatty liver disease and metabolic dysfunction-associated steatotic liver disease (MASLD). Wild-type and FKBP5-knockout (FKKO) mice were fed a normal chow diet or a high-fat diet for 16 weeks. Mouse GM was examined using 16\u00a0S rRNA metagenomic analysis. The number of gut-liver immune cells was measured using flow cytometry. HFD-induced hepatic steatosis and inflammation were prevented in FKBP5-deficient mice. FKKO animals showed higher butyric acid levels and GM resistance to diet-induced obesity alterations according to 16\u00a0S ribosomal rRNA gene analysis and displayed an HFD-specific gut-liver immunological response that maintained gut barrier failure and mucosal immunity, which are important for GM homeostasis. FKBP5 helps the GM address inadequate immunological responses, including lower gut and liver CD11b\n                    <jats:sup>+<\/jats:sup>\n                    Ly6C\n                    <jats:sup>+<\/jats:sup>\n                    monocytes and neutrophils, and protects against obesity by improving the GM response to HFD-induced MASLD. FKBP5 protects against HFD-induced MASLD through metabolic coordination between the gut barrier and intrahepatic immunity.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-38549-w","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T14:15:23Z","timestamp":1771251323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RETRACTED ARTICLE: FK506-binding protein-5 in high-fat diet-induced metabolic dysfunction-associated steatotic liver disease"],"prefix":"10.1038","volume":"16","author":[{"given":"Li-Ling","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jen","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Hao","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luen-Kui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Chang","family":"Juan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"38549_CR1","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1002\/cmdc.201200137","volume":"7","author":"MV Schmidt","year":"2012","unstructured":"Schmidt, M. V., Paez-Pereda, M., Holsboer, F. & Hausch, F. The prospect of FKBP51 as a drug target. Chem. Med. Chem. 7, 1351\u20131359. https:\/\/doi.org\/10.1002\/cmdc.201200137 (2012).","journal-title":"Chem. Med. Chem."},{"key":"38549_CR2","doi-asserted-by":"publisher","unstructured":"Zannas AS, Wiechmann T, Gassen NC, Binder EB. Gene-Stress-Epigenetic Regulation of FKBP5: Clinical and Translational Implications. Neuropsychopharmacology 41(1):261-74. https:\/\/doi.org\/10.1038\/npp.2015.235 (2016).","DOI":"10.1038\/npp.2015.235"},{"key":"38549_CR3","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1038\/s41467-017-01783-y","volume":"8","author":"G Balsevich","year":"2017","unstructured":"Balsevich, G. et al. Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function. Nat. Commun. 8, 1725. https:\/\/doi.org\/10.1038\/s41467-017-01783-y (2017).","journal-title":"Nat. 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Please see the Retraction Notice for more detail:","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-026-69443-0","URL":"https:\/\/doi.org\/10.1038\/s41598-026-69443-0","order":9,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"9241"}}