title: Specific microbiome changes in a mouse model of parenteral nutrition associated liver injury and intestinal inflammation.
abstract: BACKGROUND
  Parenteral nutrition (PN) has been a life-saving treatment in infants intolerant of enteral feedings. However, PN is associated with liver injury (PN Associated Liver Injury: PNALI) in a significant number of PN-dependent infants. We have previously reported a novel PNALI mouse model in which PN infusion combined with intestinal injury results in liver injury. In this model, lipopolysaccharide activation of toll-like receptor 4 signaling, soy oil-derived plant sterols, and pro-inflammatory activation of Kupffer cells (KCs) played key roles. The objective of this study was to explore changes in the intestinal microbiome associated with PNALI.
  
  
  RESULTS
  Microbiome analysis in the PNALI mouse identified specific alterations within colonic microbiota associated with PNALI and further association of these communities with the lipid composition of the PN solution. Intestinal inflammation or soy oil-based PN infusion alone (in the absence of enteral feeds) caused shifts within the gut microbiota. However, the combination resulted in accumulation of a specific taxon, Erysipelotrichaceae (23.8% vs. 1.7% in saline infused controls), in PNALI mice. Moreover, PNALI was markedly attenuated by enteral antibiotic treatment, which also was associated with significant reduction of Erysipelotrichaceae (0.6%) and a Gram-negative constituent, the S24-7 lineage of Bacteroidetes (53.5% in PNALI vs. 0.8%). Importantly, removal of soy oil based-lipid emulsion from the PN solution resulted in significant reduction of Erysipelotrichaceae as well as attenuation of PNALI. Finally, addition of soy-derived plant sterol (stigmasterol) to fish oil-based PN restored Erysipelotrichaceae abundance and PNALI.
  
  
  CONCLUSIONS
  Soy oil-derived plant sterols and the associated specific bacterial groups in the colonic microbiota are associated with PNALI. Products from these bacteria may directly trigger activation of KCs and promote PNALI. Furthermore, the results indicate that lipid modification of PN solutions may alter specific intestinal bacterial species associated with PNALI, and thus suggest strategies for management of PNALI.
authors.affiliation: Department of Pediatrics, Section of Pulmonary Medicine, University of Colorado, Aurora, Colorado, United States of America.
authors.forename: J Kirk
authors.initials: JK
authors.lastname: Harris
authors.affiliation: Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Karim C
authors.initials: KC
authors.lastname: El Kasmi
authors.affiliation: Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Anderson
authors.affiliation: Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Devereaux
authors.affiliation: Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Fillon
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, United States of America.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Robertson
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Brandie D
authors.initials: BD
authors.lastname: Wagner
authors.affiliation: Department of Pediatrics, Section of Pulmonary Medicine, University of Colorado, Aurora, Colorado, United States of America.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Stevens
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, United States of America.
authors.forename: Norman R
authors.initials: NR
authors.lastname: Pace
authors.affiliation: Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Sokol
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D007728:Kupffer Cells / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000293:injuries* / Q000382:microbiology*; D008297:Male; D051379:Mice; D064307:Microbiota; D010288:Parenteral Nutrition / Q000009:adverse effects*; D010938:Plant Oils / Q000494:pharmacology; D013025:Glycine max / Q000737:chemistry
chemical_list: D010938:Plant Oils