title: Unravelling the metabolic impact of SBS-associated microbial dysbiosis: Insights from the piglet short bowel syndrome model.
abstract: Liver disease is a major source of morbidity and mortality in children with short bowel syndrome (SBS). SBS-associated microbial dysbiosis has recently been implicated in the development of SBS-associated liver disease (SBS-ALD), however the pathological implications of this association have not been explored. In this study high-throughput sequencing of colonic content from the well-validated piglet SBS-ALD model was examined to determine alterations in microbial communities, and concurrent metabolic alterations identified in urine samples via targeted mass spectrometry approaches (GC-MS, LC-MS, FIA-MS) further uncovered impacts of microbial disturbance on metabolic outcomes in SBS-ALD. Multi-variate analyses were performed to elucidate contributing SBS-ALD microbe and metabolite panels and to identify microbe-metabolite interactions. A unique SBS-ALD microbe panel was clearest at the genus level, with discriminating bacteria predominantly from the Firmicutes and Bacteroidetes phyla. The SBS-ALD metabolome included important alterations in the microbial metabolism of amino acids and the mitochondrial metabolism of branched chain amino acids. Correlation analysis defined microbe-metabolite clustering patterns unique to SBS-ALD and identified a metabolite panel that correlates with dysbiosis of the gut microbiome in SBS.
authors.affiliation: Intestinal Failure and Clinical Nutrition Group, Murdoch Childrens Research Institute, Parkville, Australia.
authors.forename: Prue M
authors.initials: PM
authors.lastname: Pereira-Fantini
authors.affiliation: Centre for Systems Genomics, School of Biosciences, The University of Melbourne, Parkville, Australia.|Department of Pathology, The University of Melbourne, Parkville, Australia.
authors.forename: Sean G
authors.initials: SG
authors.lastname: Byars
authors.affiliation: Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Parkville, Australia.|Department of Paediatrics, University of Melbourne, Parkville, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Pitt
authors.affiliation: Intestinal Failure and Clinical Nutrition Group, Murdoch Childrens Research Institute, Parkville, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Lapthorne
authors.affiliation: Teagasc Food Research Centre, Moorepark, Fermoy, Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: Fouhy
authors.affiliation: Teagasc Food Research Centre, Moorepark, Fermoy, Ireland.|APC Microbiome Institute, Cork, Ireland.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Cotter
authors.affiliation: Intestinal Failure and Clinical Nutrition Group, Murdoch Childrens Research Institute, Parkville, Australia.|Department of Paediatrics, University of Melbourne, Parkville, Australia.|Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, Australia.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Bines
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003106:Colon / Q000382:microbiology; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000150:complications*; D000069196:Gastrointestinal Microbiome; D008107:Liver Diseases / Q000473:pathology*; D013058:Mass Spectrometry; D055442:Metabolome; D012778:Short Bowel Syndrome / Q000150:complications* / Q000382:microbiology*; D013552:Swine; D016482:Urinalysis; D014556:Urine / Q000737:chemistry