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

D T Reid, B McDonald, T Khalid, T Vo, L P Schenck, M G Surette, P L Beck, R A Reimer, C S Probert, K P Rioux, B Eksteen

Research output: Contribution to journalArticle (Academic Journal)

Abstract

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.

Original languageEnglish
Pages (from-to)1337-44
Number of pages8
JournalBiochimica et Biophysica Acta (BBA)
Volume1862
Issue number7
DOIs
Publication statusPublished - Jul 2016

Bibliographical note

Copyright © 2016 Elsevier B.V. All rights reserved.

Keywords

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

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  • Cite this

    Reid, D. T., McDonald, B., Khalid, T., Vo, T., Schenck, L. P., Surette, M. G., Beck, P. L., Reimer, R. A., Probert, C. S., Rioux, K. P., & Eksteen, B. (2016). Unique microbial-derived volatile organic compounds in portal venous circulation in murine non-alcoholic fatty liver disease. Biochimica et Biophysica Acta (BBA), 1862(7), 1337-44. https://doi.org/10.1016/j.bbadis.2016.04.005