{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:45:22Z","timestamp":1793306722004,"version":"4.5.0"},"reference-count":44,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK131064-01"],"award-info":[{"award-number":["1R01DK131064-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["2R01DK117965-06A"],"award-info":[{"award-number":["2R01DK117965-06A"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jlr.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Lipid Research"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.jlr.2025.100936","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:19:38Z","timestamp":1762388378000},"page":"100936","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Gly-\u03b2-muricholic acid and FGF15 combination therapy synergistically reduces \u201chumanized\u201d bile acid pool toxicity in cholestasis mice"],"prefix":"10.1016","volume":"66","author":[{"given":"Mohammad Nazmul","family":"Hasan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2518-9519","authenticated-orcid":false,"given":"Lijie","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiangang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jlr.2025.100936_bib1","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1056\/NEJM199810223391707","article-title":"Molecular pathogenesis of cholestasis","volume":"339","author":"Trauner","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.jlr.2025.100936_bib2","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.2174\/092986706778521823","article-title":"Modulation of hepatocyte apoptosis: cross-talk between bile acids and nuclear steroid receptors","volume":"13","author":"Sola","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.jlr.2025.100936_bib3","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1053\/j.gastro.2005.12.029","article-title":"Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid","volume":"130","author":"Pares","year":"2006","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jlr.2025.100936_bib4","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/hep.22428","article-title":"Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis","volume":"48","author":"Corpechot","year":"2008","journal-title":"Hepatology"},{"key":"10.1016\/j.jlr.2025.100936_bib5","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1021\/jm025529g","article-title":"6alpha-ethyl- acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity","volume":"45","author":"Pellicciari","year":"2002","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jlr.2025.100936_bib6","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1053\/j.gastro.2014.12.005","article-title":"Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid","volume":"148","author":"Hirschfield","year":"2015","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jlr.2025.100936_bib7","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1002\/hep.29569","article-title":"A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis","volume":"67","author":"Kowdley","year":"2018","journal-title":"Hepatology"},{"key":"10.1016\/j.jlr.2025.100936_bib8","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A placebo-controlled trial of obeticholic acid in primary biliary cholangitis","volume":"375","author":"Nevens","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.jlr.2025.100936_bib9","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1124\/pr.113.008201","article-title":"Bile acid signaling in metabolic disease and drug therapy","volume":"66","author":"Li","year":"2014","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.jlr.2025.100936_bib10","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1194\/jlr.M071183","article-title":"Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans","volume":"57","author":"Takahashi","year":"2016","journal-title":"J. Lipid. Res."},{"key":"10.1016\/j.jlr.2025.100936_bib11","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1194\/jlr.RA119000395","article-title":"Regulation of bile acid metabolism in mouse models with hydrophobic bile acid composition","volume":"61","author":"Honda","year":"2020","journal-title":"J. Lipid. Res."},{"key":"10.1016\/j.jlr.2025.100936_bib12","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jcmgh.2020.12.004","article-title":"Cholangiopathy and biliary fibrosis in Cyp2c70-Deficient mice are fully reversed by ursodeoxycholic acid","volume":"11","author":"de Boer","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"10.1016\/j.jlr.2025.100936_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.jlr.2023.100340","article-title":"Combining ASBT inhibitor and FGF15 treatments enhances therapeutic efficacy against cholangiopathy in female but not male Cyp2c70 KO mice","volume":"64","author":"Hasan","year":"2023","journal-title":"J. Lipid. Res."},{"key":"10.1016\/j.jlr.2025.100936_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.jlr.2022.100261","article-title":"Ileal bile acid transporter inhibition in Cyp2c70 KO mice ameliorates cholestatic liver injury","volume":"63","author":"Truong","year":"2022","journal-title":"J. Lipid. Res."},{"key":"10.1016\/j.jlr.2025.100936_bib15","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/hep4.1209","article-title":"NGM282 for treatment of patients with primary biliary cholangitis: a multicenter, randomized, double-blind, placebo-controlled trial","volume":"2","author":"Mayo","year":"2018","journal-title":"Hepatol. Commun."},{"key":"10.1016\/j.jlr.2025.100936_bib16","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jhep.2018.10.035","article-title":"Effect of NGM282, an FGF19 analogue, in primary sclerosing cholangitis: a multicenter, randomized, double-blind, placebo-controlled phase II trial","volume":"70","author":"Hirschfield","year":"2019","journal-title":"J. Hepatol."},{"key":"10.1016\/j.jlr.2025.100936_bib17","article-title":"Potent suppression of hydrophobic bile acids by aldafermin, an FGF19 analogue, across metabolic and cholestatic liver diseases","volume":"3","author":"Sanyal","year":"2021","journal-title":"JHEP Rep."},{"key":"10.1016\/j.jlr.2025.100936_bib18","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1002\/hep4.1980","article-title":"Maralixibat for the treatment of PFIC: long-term, IBAT inhibition in an open-label, phase 2 study","volume":"6","author":"Loomes","year":"2022","journal-title":"Hepatol. Commun."},{"key":"10.1016\/j.jlr.2025.100936_bib19","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1002\/hep.28257","article-title":"Engineered fibroblast growth factor 19 reduces liver injury and resolves sclerosing cholangitis in Mdr2-deficient mice","volume":"63","author":"Zhou","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.jlr.2025.100936_bib20","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/hep.27973","article-title":"Pharmacological inhibition of apical sodium-dependent bile acid transporter changes bile composition and blocks progression of sclerosing cholangitis in multidrug resistance 2 knockout mice","volume":"63","author":"Miethke","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.jlr.2025.100936_bib21","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.jhep.2015.10.024","article-title":"Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis","volume":"64","author":"Baghdasaryan","year":"2016","journal-title":"J. Hepatol."},{"key":"10.1016\/j.jlr.2025.100936_bib22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1159\/000450988","article-title":"Apical sodium-dependent transporter inhibitors in primary biliary cholangitis and primary sclerosing cholangitis","volume":"35","author":"Hegade","year":"2017","journal-title":"Dig. Dis."},{"key":"10.1016\/j.jlr.2025.100936_bib23","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.3390\/cells12101371","article-title":"Glycine-beta-Muricholic acid improves liver fibrosis and gut barrier function by reducing bile acid pool size and hydrophobicity in Male Cyp2c70 knockout mice","volume":"12","author":"Hasan","year":"2023","journal-title":"Cells"},{"key":"10.1016\/j.jlr.2025.100936_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.jlr.2024.100649","article-title":"Gly-beta-MCA is a potent anti-cholestasis agent against \"human-like\" hydrophobic bile acid-induced biliary injury in mice","volume":"65","author":"Hasan","year":"2024","journal-title":"J. Lipid. Res."},{"key":"10.1016\/j.jlr.2025.100936_bib25","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms10166","article-title":"Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction","volume":"6","author":"Jiang","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jlr.2025.100936_bib26","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S0022-2275(20)38331-0","article-title":"Quantitative estimation of the hydrophilic-hydrophobic balance of mixed bile salt solutions","volume":"30","author":"Heuman","year":"1989","journal-title":"J. Lipid. Res."},{"key":"10.1016\/j.jlr.2025.100936_bib27","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.3748\/wjg.15.5326","article-title":"Usefulness of a scoring system in the interpretation of histology in neonatal cholestasis","volume":"15","author":"Lee","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.jlr.2025.100936_bib28","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.jcmgh.2021.04.013","article-title":"Combined ASBT inhibitor and FGF15 treatment improves therapeutic efficacy in experimental nonalcoholic steatohepatitis","volume":"12","author":"Matye","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"10.1016\/j.jlr.2025.100936_bib29","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1002\/hep4.1108","article-title":"Engineered FGF19 eliminates bile acid toxicity and lipotoxicity leading to resolution of steatohepatitis and fibrosis in mice","volume":"1","author":"Zhou","year":"2017","journal-title":"Hepatol. Commun."},{"key":"10.1016\/j.jlr.2025.100936_bib30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.cmet.2005.09.001","article-title":"Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis","volume":"2","author":"Inagaki","year":"2005","journal-title":"Cell. Metab."},{"key":"10.1016\/j.jlr.2025.100936_bib31","doi-asserted-by":"crossref","first-page":"G476","DOI":"10.1152\/ajpgi.00430.2005","article-title":"The nuclear receptor for bile acids, FXR, transactivates human organic solute transporter-alpha and -beta genes","volume":"290","author":"Landrier","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver. Physiol."},{"key":"10.1016\/j.jlr.2025.100936_bib32","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S1097-2765(00)00051-4","article-title":"A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis","volume":"6","author":"Goodwin","year":"2000","journal-title":"Mol. Cell."},{"key":"10.1016\/j.jlr.2025.100936_bib33","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1053\/gast.2001.25503","article-title":"The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp","volume":"121","author":"Denson","year":"2001","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jlr.2025.100936_bib34","doi-asserted-by":"crossref","first-page":"28857","DOI":"10.1074\/jbc.M011610200","article-title":"Human bile salt export pump promoter is transactivated by the farnesoid X receptor\/bile acid receptor","volume":"276","author":"Ananthanarayanan","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jlr.2025.100936_bib35","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.3390\/metabo13101043","article-title":"Lactobacillus johnsonii attenuates liver steatosis and bile acid dysregulation in parenteral nutrition-fed rats","volume":"13","author":"Xu","year":"2023","journal-title":"Metabolites"},{"key":"10.1016\/j.jlr.2025.100936_bib36","article-title":"Postbiotics from Lactobacillus Johnsonii activates gut innate immunity to mitigate alcohol-associated liver disease","volume":"12","author":"Yin","year":"2024","journal-title":"Adv. Sci. (Weinh)"},{"key":"10.1016\/j.jlr.2025.100936_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodchem.2022.134643","article-title":"Dietary Lactobacillus reuteri prevent from inflammation mediated apoptosis of liver via improving intestinal microbiota and bile acid metabolism","volume":"404","author":"Lin","year":"2023","journal-title":"Food. Chem."},{"key":"10.1016\/j.jlr.2025.100936_bib38","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241311010","article-title":"Combined inhibition of the TGF-beta1\/Smad pathway by Prevotella copri and Lactobacillus murinus to reduce inflammation and fibrosis in primary sclerosing cholangitis","volume":"24","author":"Shen","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jlr.2025.100936_bib39","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3389\/fcimb.2015.00084","article-title":"Insights into the role of Erysipelotrichaceae in the human host","volume":"5","author":"Kaakoush","year":"2015","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10.1016\/j.jlr.2025.100936_bib40","first-page":"261","article-title":"Gut microbiota in liver disease: what do we know and what do we not know?","volume":"35","author":"Jiang","year":"2020","journal-title":"Physiology (Bethesda)"},{"key":"10.1016\/j.jlr.2025.100936_bib41","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1111\/j.1478-3231.2010.02270.x","article-title":"Clinical significance of Staphylococcus aureus infection in patients with chronic liver diseases","volume":"30","author":"Kang","year":"2010","journal-title":"Liver. Int."},{"key":"10.1016\/j.jlr.2025.100936_bib42","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1042\/CS20230413","article-title":"Absence of gut microbiota reduces neonatal survival and exacerbates liver disease in Cyp2c70-deficient mice with a human-like bile acid composition","volume":"137","author":"Sjoland","year":"2023","journal-title":"Clin. Sci. (Lond)"},{"key":"10.1016\/j.jlr.2025.100936_bib43","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/s41586-023-06990-w","article-title":"Bile salt hydrolase catalyses formation of amine-conjugated bile acids","volume":"626","author":"Rimal","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.jlr.2025.100936_bib44","doi-asserted-by":"crossref","first-page":"G45","DOI":"10.1152\/ajpgi.00044.2025","article-title":"Gly-betaMCA modulates bile acid metabolism to reduce hepatobiliary injury in Mdr2 KO mice","volume":"329","author":"Hasan","year":"2025","journal-title":"Am. J. Physiol. Gastrointest. Liver. Physiol."}],"container-title":["Journal of Lipid Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022227525001993?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022227525001993?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T16:40:46Z","timestamp":1766076046000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022227525001993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":44,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["S0022227525001993"],"URL":"https:\/\/doi.org\/10.1016\/j.jlr.2025.100936","relation":{},"ISSN":["0022-2275"],"issn-type":[{"value":"0022-2275","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Gly-\u03b2-muricholic acid and FGF15 combination therapy synergistically reduces \u201chumanized\u201d bile acid pool toxicity in cholestasis mice","name":"articletitle","label":"Article Title"},{"value":"Journal of Lipid Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jlr.2025.100936","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology\u00e9","name":"copyright","label":"Copyright"}],"article-number":"100936"}}