Rapid Postnatal Upregulation of Intestinal FXR-FGF19 Signalling in Premature Pigs

OBJECTIVES: Bile acid (BA) homeostasis is regulated by intestinal cellular signaling involving the farnesoid X receptor (FXR) and fibroblast growth factor 19 (FGF19) secretion. Using preterm and term pigs as a model, we examined postnatal changes in expression of the FXR-FGF19 axis that is poorly characterized in human infants. METHODS: Pigs delivered by cesarean-section at 10 d preterm and near full term (115 d gestation) were fitted with orogastric and umbilical arterial catheters. Pigs were fed combined parenteral nutrition and minimal enteral nutrition for 5 d, followed by milk formula until 26 d. Plasma and tissue samples were collected at d 0, 5, 11, and 26. Plasma FGF19 concentration and liver and distal intestinal gene expression of FGF19 and other FXR target genes were quantified. RESULTS: Plasma FGF19 levels were lower in preterm vs. term newborn pigs (P < 0.05), increased markedly by 5 d, especially in preterm pigs, and decreased in both groups until d 26. Likewise, intestinal FXR and FGF19 expression was lower (P