The Farnesoid X Receptor Agonist Tropifexor Prevents Liver Damage in Parenteral Nutrition‐fed Neonatal Piglets

• Published in: Journal of pediatric gastroenterology and nutrition Vol. 73; no. 1; pp. e11 - e19
• Main Authors: Liu, Yang, Xiao, Yongtao, Chen, Shanshan, Tian, Xinbei, Wang, Weipeng, Wang, Ying, Cai, Wei
• Format: Journal Article
• Language: English
• Published: United States 01.07.2021
• Subjects: farnesoid X receptor; liver disease; neonatal piglet; parenteral nutrition; tropifexor
• ISSN: 0277-2116; 1536-4801
• DOI: 10.1097/MPG.0000000000003135

ABSTRACT Objectives: Intestinal failure‐associated liver disease (IFALD) is a life‐threatening complication for patients with intestinal failure who receive long‐term parenteral nutrition (PN). We evaluated the effects of the farnesoid X receptor agonist tropifexor on a neonatal piglet model of IFALD fed with PN. Methods: The piglets received PN and tropifexor for 14 days, then levels of liver enzymes, bile acid metabolism, inflammation, and intestinal barrier markers were assessed using quantitative real‐time PCR. Fibroblast growth factor (FGF) 19 serum levels were determined using enzyme‐linked immunosorbent assays. Bile acids were determined in liver, serum, and intestinal contents, and the microbiome was sequenced in different intestinal segments. Results: The PN model was established in newborn piglets. The levels of serum liver enzymes, pro‐inflammatory factors, and oxidative stress increased in the livers of piglets fed with PN, but not in those fed with PN and tropifexor. Tropifexor stimulated FGF19 expression in ileal epithelial cells, increased portal FGF19 levels, then inhibited cholesterol 7α‐hydroxylase expression in the liver. Tropifexor increased the relative abundance of bacteria associated with bile salt hydrolase and 7α‐dehydrogenation in the contents of ileum and altered the composition of bile acids in serum, liver, and intestinal contents. Tropifexor also inhibited intestinal inflammation, alleviated intestinal mucosal atrophy, and improved the intestinal barrier. Conclusions: Tropifexor might prevent liver damage in neonatal piglets receiving PN by altering the composition of intestinal microbiota and bile acids. Tropifexor also alleviates intestinal inflammation and preserves the intestinal barrier.