{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:28:35Z","timestamp":1792700915925,"version":"4.5.0"},"reference-count":62,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01CA179582"],"award-info":[{"award-number":["U01CA179582"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dysregulated bile acid (BA) synthesis or reduced farnesoid X receptor (FXR) levels are found in patients having metabolic diseases, autoimmune hepatitis, and liver cirrhosis or cancer. The objective of this study was to establish the relationship between butyrate and dysregulated BA synthesis\u2010induced hepatitis as well as the effect of butyrate in reversing the liver pathology. Wild\u2010type (WT) and FXR knockout (KO) male mice were placed on a control (CD) or western diet (WD) for 15 months. In the presence or absence of butyrate supplementation, feces obtained from 15\u2010month\u2010old WD\u2010fed FXR KO mice, which had severe hepatitis and liver tumors, were transplanted to 7\u2010month\u2010old WD\u2010fed FXR KO for 3 months. Hepatic phenotypes, microbiota profile, and BA composition were analyzed. Butyrate\u2010generating bacteria and colonic butyrate concentration were reduced due to FXR inactivation and further reduced by WD intake. In addition, WD\u2010fed FXR KO male mice had the highest concentration of hepatic \u03b2\u2010muricholic acid (\u03b2\u2010MCA) and bacteria\u2010generated deoxycholic acid (DCA) accompanied by serious hepatitis. Moreover, dysregulated BA and reduced SCFA signaling co\u2010existed in both human liver cancers and WD\u2010fed FXR KO mice. Microbiota transplantation using butyrate\u2010deficient feces derived from 15\u2010month\u2010old WD\u2010fed FXR KO mice increased hepatic lymphocyte numbers as well as hepatic \u03b2\u2010MCA and DCA concentrations. Furthermore, butyrate supplementation reduced hepatic \u03b2\u2010MCA as well as DCA and eliminated hepatic lymphocyte infiltration. In conclusion, reduced butyrate contributes to the development of hepatitis in the FXR KO mouse model. In addition, butyrate reverses dysregulated BA synthesis and its associated hepatitis. Copyright \u00a9 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4983","type":"journal-article","created":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T11:46:44Z","timestamp":1505130404000},"page":"431-441","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation"],"prefix":"10.1002","volume":"243","author":[{"given":"Lili","family":"Sheng","sequence":"first","affiliation":[{"name":"Department of Medical Pathology and Laboratory Medicine University of California, Davis  Sacramento CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasant Kumar","family":"Jena","sequence":"additional","affiliation":[{"name":"Department of Medical Pathology and Laboratory Medicine University of California, Davis  Sacramento CA 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