The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice

Alida Kindt, Gerhard Liebisch, Thomas Clavel, Dirk Haller, Gabriele Hörmannsperger, Hongsup Yoon, Daniela Kolmeder, Alexander Sigruener, Sabrina Krautbauer, Claudine Seeliger, Alexandra Ganzha, Sabine Schweizer, Rosalie Morisset, Till Strowig, Hannelore Daniel, Dominic Helm, Bernhard Küster, Jan Krumsiek () and Josef Ecker ()
Additional contact information
Alida Kindt: Helmholtz Zentrum München
Gerhard Liebisch: Universitätsklinikum Regensburg
Thomas Clavel: Universitätsklinikum Aachen
Dirk Haller: Technische Universität München (TUM)
Gabriele Hörmannsperger: Technische Universität München (TUM)
Hongsup Yoon: Technische Universität München (TUM)
Daniela Kolmeder: Technische Universität München (TUM)
Alexander Sigruener: Universitätsklinikum Regensburg
Sabrina Krautbauer: Universitätsklinikum Regensburg
Claudine Seeliger: Technische Universität München (TUM)
Alexandra Ganzha: Technische Universität München (TUM)
Sabine Schweizer: Technische Universität München (TUM)
Rosalie Morisset: Technische Universität München (TUM)
Till Strowig: Helmholtz Centre for Infection Research
Hannelore Daniel: Technische Universität München (TUM)
Dominic Helm: Technische Universität München (TUM)
Bernhard Küster: Technische Universität München (TUM)
Jan Krumsiek: Helmholtz Zentrum München
Josef Ecker: Technische Universität München (TUM)

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Interactions between the gut microbial ecosystem and host lipid homeostasis are highly relevant to host physiology and metabolic diseases. We present a comprehensive multi-omics view of the effect of intestinal microbial colonization on hepatic lipid metabolism, integrating transcriptomic, proteomic, phosphoproteomic, and lipidomic analyses of liver and plasma samples from germfree and specific pathogen-free mice. Microbes induce monounsaturated fatty acid generation by stearoyl-CoA desaturase 1 and polyunsaturated fatty acid elongation by fatty acid elongase 5, leading to significant alterations in glycerophospholipid acyl-chain profiles. A composite classification score calculated from the observed alterations in fatty acid profiles in germfree mice clearly differentiates antibiotic-treated mice from untreated controls with high sensitivity. Mechanistic investigations reveal that acetate originating from gut microbial degradation of dietary fiber serves as precursor for hepatic synthesis of C16 and C18 fatty acids and their related glycerophospholipid species that are also released into the circulation.

Date: 2018
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DOI: 10.1038/s41467-018-05767-4

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