{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:14:15Z","timestamp":1791861255266,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The study aims to investigate the mechanism of Farnesoid X receptor (FXR) activation in sepsis\u2010induced abnormal bile acid metabolism and the metabolism status of each bile acid type.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The sepsis mouse model was developed via lipopolysaccharide intraperitoneal injection and confirmed via hematoxylin and eosin (H&amp;E) staining. FXR agonist activated the FXR\/fibroblast growth factor (FGF)15\/FGFR pathway via quantitative real\u2010time polymerase chain reaction and Western blot. Consequently, metabolomics and bioinformatics analysis were conducted to identify the alterations in each kind of bile acid content following FXR agonist\/inhibitor intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The H&amp;E staining indicated that FXR activation alleviates the liver injury of the sepsis mouse model. The increased FGF15 and FXFR expression levels and decreased CYP7A1 demonstrated FXR\/FGF15\/FGFR pathway activation following FXR agonist treatment. Furthermore, total bile acid, interleukin (IL)\u20106, and tumor necrosis factor\u2010\u03b1 concentrations were downregulated after FXR activation, whereas IL\u201010 concentration was upregulated, indicating the alleviated effect of FXR agonist in sepsis. Consequently, metabolomics and bioinformatics analysis determined that T\u2010a\u2010MCA were downregulated in both FXR agonist and inhibitor groups, whereas six bile acid types were altered in the control group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FXR activation was crucial in alleviating sepsis\u2010induced hepatic injury and cholestasis through the FGF15\/FGFR signaling pathway, and FXR may act as a potential preventive and intervention target of sepsis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70155","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T09:21:18Z","timestamp":1744017678000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Farnesoid X Receptor Regulated Sepsis\u2010Induced Abnormal Bile Acid Metabolism via the Fibroblast Growth Factor 15\/Fibroblast Growth Factor Receptor 4 Pathway"],"prefix":"10.1002","volume":"13","author":[{"given":"Ziyang","family":"Zhou","sequence":"first","affiliation":[{"name":"Trauma\u2010Emergency &amp; Critical Care Medicine Center Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[{"name":"Trauma\u2010Emergency &amp; Critical Care Medicine Center Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liou","family":"Huang","sequence":"additional","affiliation":[{"name":"Trauma\u2010Emergency &amp; Critical Care Medicine Center Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai 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