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

作者：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^*

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2016, 1862(7): 1337-1344.

DOI：10.1016/j.bbadis.2016.04.005

• Volatile organic compounds
• Liver
• Microbiome
• Metabolomics

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 microbiotaderived 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.

• 出版日期2016-7