Altered FXR signalling is associated with bile acid dysmetabolism in short bowel syndrome-associated liver disease
Prue M Pereira-Fantini, Susan Lapthorne, Susan A Joyce, Nicole L Dellios, Guineva Wilson, Fiona Fouhy, Sarah L Thomas, Michelle Scurr, Colin Hill, Cormac GM Gahan, Paul D Cotter, Peter J Fuller, Winita Hardikar, Julie E Bines
JOURNAL OF HEPATOLOGY | ELSEVIER | Published : 2014
BACKGROUND & AIMS: Despite the mortality associated with liver disease observed in patients with short bowel syndrome (SBS), mechanisms underlying the development of SBS-associated liver disease (SBS-ALD) are poorly understood. This study examines the impact of bacterially-mediated bile acid (BA) dysmetabolism on farnesoid X receptor (FXR) signalling pathways and clinical outcome in a piglet model of SBS-ALD. METHODS: 4-week old piglets underwent 75% small bowel resection (SBR) or sham operation. Liver histology and hepatic inflammatory gene expression were examined. Abundance of BA biotransforming bacteria was determined and metabolomic studies detailed the alterations in BA composition of ..View full abstract
Awarded by Science Foundation of Ireland (Alimentary Pharmabiotic Centre)
Awarded by National Health and Medical Research Council of Australia
The MCRI and Prince Henry's Institute are supported by the Victorian Government's Operational Infrastructure support program. SAJ, CH, PC, and CGMG are supported in part by grants from the Science Foundation of Ireland in the form of a centre grant (Alimentary Pharmabiotic Centre; Grant Numbers SFI/12/RC/2273 and 12/RC/2273) and a PI grand to PCR (11/PI/1137). PJF is supported by a Senior Principal research fellowship from the National Health and Medical Research Council of Australia (#1002559). FF is in receipt of an Irish Research Council EMBARK scholarship and is a Teagasc Walsk Fellow.