title: Unique microbial-derived volatile organic compounds in portal venous circulation in murine non-alcoholic fatty liver disease.
abstract: Non-alcoholic fatty liver disease is now the leading liver disease in North America. The progression of non-alcoholic fatty liver disease to the inflammatory condition, non-alcoholic steatohepatitis is complex and currently not well understood. Intestinal microbial dysbiosis has been implicated in the development of non-alcoholic fatty liver disease and progression of non-alcoholic steatohepatitis. Volatile organic compounds are byproducts of microbial metabolism in the gut that may enter portal circulation and have hepatotoxic effects contributing to the pathogenesis of non-alcoholic steatohepatitis. To test this hypothesis, we measured volatile organic compounds in cecal luminal contents and portal venous blood in a mouse model of non-alcoholic steatohepatitis.
  
  
  
  Gas chromatography-mass spectrometry analysis was conducted on cecal content and portal vein blood for volatile organic compound detection from mice fed a methionine and choline deficient diet, which induces non-alcoholic steatohepatitis. The colonic microbiome was studied by 16S rRNA gene amplification using the Illumina MiSeq platform.
  
  
  
  Sixty-eight volatile organic compounds were detected in cecal luminal content, a subset of which was also present in portal venous blood. Importantly, differences in portal venous volatile organic compounds were associated with diet-induced steatohepatitis establishing a biochemical link between gut microbiota-derived volatile organic compounds and increased susceptibility to non-alcoholic steatohepatitis.
  
  
  
  Our model creates a novel tool to further study the role of gut-derived volatile organic compounds in the pathogenesis of non-alcoholic steatohepatitis.
authors.affiliation: Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: D T
authors.initials: DT
authors.lastname: Reid
authors.affiliation: Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada; Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.
authors.forename: B
authors.initials: B
authors.lastname: McDonald
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: T
authors.initials: T
authors.lastname: Khalid
authors.affiliation: Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Vo
authors.affiliation: Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: L P
authors.initials: LP
authors.lastname: Schenck
authors.affiliation: Department of Medicine, Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: M G
authors.initials: MG
authors.lastname: Surette
authors.affiliation: Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: P L
authors.initials: PL
authors.lastname: Beck
authors.affiliation: Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada; Faculty of Kinesiology, University of Calgary, Calgary, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Reimer
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: C S
authors.initials: CS
authors.lastname: Probert
authors.affiliation: Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada; Department of Medicine, Division of Gastroenterology and Hepatology, Department of Microbiology and Infectious Diseases, Gastrointestinal Research Group, University of Calgary, Calgary, Canada.
authors.forename: K P
authors.initials: KP
authors.lastname: Rioux
authors.affiliation: Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada. Electronic address: b.eksteen@ucalgary.ca.
authors.forename: B
authors.initials: B
authors.lastname: Eksteen
mesh_terms: D000818:Animals; D001419:Bacteria / Q000302:isolation & purification; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007249:Inflammation / Q000382:microbiology* / Q000473:pathology; D018836:Inflammation Mediators / Q000032:analysis; D008099:Liver / Q000098:blood supply* / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000382:microbiology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D064307:Microbiota; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000382:microbiology* / Q000473:pathology; D011169:Portal Vein / Q000382:microbiology* / Q000473:pathology; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D018836:Inflammation Mediators; D055549:Volatile Organic Compounds
keywords: Liver; Metabolomics; Microbiome; Volatile organic compounds