{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:05:53Z","timestamp":1785927953620,"version":"3.56.0"},"posted":{"date-parts":[[2024,9,7]]},"group-title":"Physiology","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,7]],"date-time":"2024-09-07T00:00:00Z","timestamp":1725667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND &amp; AIMS<\/jats:title>\n                  <jats:p>We aimed to investigate the relative efficacy of feeding different bile acids in preventing PNALD in neonatal pigs.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Newborn pigs given total parenteral nutrition (TPN) combined with minimal enteral feeding of chenodeoxycholic acid (CDCA), or increasing doses of obeticholic acid (OCA) for 19 days.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Enteral OCA (5 and 15 mg\/kg), but not CDCA (30 mg\/kg) reduced blood cholestasis markers compared to TPN controls and increased bile acids in the gallbladder and intestine. Major bile acids in the liver and distal intestine were CDCA, HCA, HDCA and OCA, and their relative proportions were increased by the type of bile acid (CDCA or OCA) given enterally. High doses of OCA increased the total NR1H4-agonistic bile acid profile in the liver and intestine above 50% total bile acids. Both CDCA and OCA treatments suppressed hepatic cyp7a1 expression, but only OCA increased hepatobiliary transporters, ABCB11, ABCC$ and ABCB1. Plasma phytosterol levels were reduced and biliary levels were increased by CDCA and OCA and hepatic sterol transporters, abcg5\/8, expression were increased by OCA. Both CDCA and OCA increased plasma FGF19 and OCA increased intestinal FGF19, FABP6, and SLC51A. Both CDCA and OCA increased intestinal mucosal growth, whereas CDCA increased the plasma GLP-2, GLP-1 and GIP.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Enteral OCA prevented cholestasis and phytosterolemia by increased hepatic bile acid and sterol transport via induction of hepatobiliary transporter FXR target genes and not by suppression of bile acid synthesis genes. We also showed an intestinal trophic action of OCA that demonstrates a dual clinical benefit of FXR agonism in the prevention of PNALD in piglets.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.09.03.611073","type":"posted-content","created":{"date-parts":[[2024,9,8]],"date-time":"2024-09-08T01:00:17Z","timestamp":1725757217000},"source":"Crossref","is-referenced-by-count":2,"title":["Selective Agonism of Liver and Gut FXR Prevents Cholestasis and Intestinal Atrophy in Parenterally Fed Neonatal Pigs"],"prefix":"10.64898","author":[{"given":"Yanjun","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengfeng","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Guthrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Stoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaji","family":"Chacko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolette","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens J.","family":"Holst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose J.","family":"Pastor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio R.","family":"Ipharraguerre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8792-3339","authenticated-orcid":false,"given":"Douglas G.","family":"Burrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024091004200820000_2024.09.03.611073v1.1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-985070"},{"key":"2024091004200820000_2024.09.03.611073v1.2","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41575-019-0132-z","article-title":"Neonatal cholestasis: emerging molecular diagnostics and potential novel therapeutics","volume":"16","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2024091004200820000_2024.09.03.611073v1.3","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/sj.jp.7211686","article-title":"Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease","volume":"27","year":"2007","journal-title":"J.Perinatol"},{"key":"2024091004200820000_2024.09.03.611073v1.4","doi-asserted-by":"publisher","DOI":"10.1177\/0148607114527772"},{"key":"2024091004200820000_2024.09.03.611073v1.5","doi-asserted-by":"crossref","first-page":"e0280691","DOI":"10.1371\/journal.pone.0280691","article-title":"Efficacy and safety of ursodeoxycholic acid in children with cholestasis: A systematic review and meta-analysis","volume":"18","year":"2023","journal-title":"PLoS One"},{"key":"2024091004200820000_2024.09.03.611073v1.6","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1097\/MPG.0000000000003763","article-title":"Intestinal Failure-Associated Liver Disease and Growth Pre-and Post-Transition to a Composite Lipid Emulsion","volume":"76","year":"2023","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2024091004200820000_2024.09.03.611073v1.7","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1002\/hep.32071","article-title":"NF-kappaB Regulation of LRH-1 and ABCG5\/8 Potentiates Phytosterol Role in the Pathogenesis of Parenteral Nutrition-Associated Cholestasis","volume":"74","year":"2021","journal-title":"Hepatology"},{"key":"2024091004200820000_2024.09.03.611073v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006898"},{"key":"2024091004200820000_2024.09.03.611073v1.9","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1038\/s41467-018-03764-1","article-title":"Macrophage-derived IL-1beta\/NF-kappaB signaling mediates parenteral nutrition-associated cholestasis","volume":"9","year":"2018","journal-title":"Nat Commun"},{"key":"2024091004200820000_2024.09.03.611073v1.10","doi-asserted-by":"crossref","unstructured":"Ng K , Stoll B , Chacko S , et al. 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