Unique microbial-derived volatile organic compounds in portal venous circulation in murine non-alcoholic fatty liver disease

Biochim Biophys Acta. 2016 Jul;1862(7):1337-44. doi: 10.1016/j.bbadis.2016.04.005. Epub 2016 Apr 13.


Background and aims: 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.

Methods: 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.

Results: 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.

Conclusion: Our model creates a novel tool to further study the role of gut-derived volatile organic compounds in the pathogenesis of non-alcoholic steatohepatitis.

Keywords: Liver; Metabolomics; Microbiome; Volatile organic compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / isolation & purification
  • Cells, Cultured
  • Disease Models, Animal
  • Inflammation / microbiology*
  • Inflammation / pathology
  • Inflammation Mediators / analysis
  • Liver / blood supply*
  • Liver / microbiology
  • Liver / pathology
  • Macrophages / microbiology
  • Macrophages / pathology
  • Male
  • Mice, Inbred C57BL
  • Microbiota
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / microbiology*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Portal Vein / microbiology*
  • Portal Vein / pathology
  • Volatile Organic Compounds / analysis*


  • Inflammation Mediators
  • Volatile Organic Compounds