title: Distinct signatures of host-microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet.
abstract: A combinatory approach using metabolomics and gut microbiome analysis techniques was performed to unravel the nature and specificity of metabolic profiles related to gut ecology in obesity. This study focused on gut and liver metabolomics of two different mouse strains, the C57BL/6J (C57J) and the C57BL/6N (C57N) fed with high-fat diet (HFD) for 3 weeks, causing diet-induced obesity in C57N, but not in C57J mice. Furthermore, a 16S-ribosomal RNA comparative sequence analysis using 454 pyrosequencing detected significant differences between the microbiome of the two strains on phylum level for Firmicutes, Deferribacteres and Proteobacteria that propose an essential role of the microbiome in obesity susceptibility. Gut microbial and liver metabolomics were followed by a combinatory approach using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and ultra performance liquid chromatography time of tlight MS/MS with subsequent multivariate statistical analysis, revealing distinctive host and microbial metabolome patterns between the C57J and the C57N strain. Many taurine-conjugated bile acids (TBAs) were significantly elevated in the cecum and decreased in liver samples from the C57J phenotype likely displaying different energy utilization behavior by the bacterial community and the host. Furthermore, several metabolite groups could specifically be associated with the C57N phenotype involving fatty acids, eicosanoids and urobilinoids. The mass differences based metabolite network approach enabled to extend the range of known metabolites to important bile acids (BAs) and novel taurine conjugates specific for both strains. In summary, our study showed clear alterations of the metabolome in the gastrointestinal tract and liver within a HFD-induced obesity mouse model in relation to the host-microbial nutritional adaptation.
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Alesia
authors.initials: A
authors.lastname: Walker
authors.affiliation: Research Unit Microbe-Plant Interactions, Research Group Molecular Microbial Ecology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pfitzner
authors.affiliation: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Neschen
authors.affiliation: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Kahle
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Mourad
authors.initials: M
authors.lastname: Harir
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Marianna
authors.initials: M
authors.lastname: Lucio
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Franco
authors.initials: F
authors.lastname: Moritz
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tziotis
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Witting
authors.affiliation: Research Unit Microbe-Plant Interactions, Research Group Molecular Microbial Ecology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rothballer
authors.affiliation: Research Unit Environmental Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Engel
authors.affiliation: Research Unit Microbe-Plant Interactions, Research Group Molecular Microbial Ecology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmid
authors.affiliation: Scientific Computing Research Unit, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Endesfelder
authors.affiliation: Technische Universität München, Molecular Nutritional Medicine, Else Kröner-Fresenius Center and ZIEL Research Center for Nutrition and Food Sciences, Freising-Weihenstephan, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
authors.affiliation: Department of Computational Systems Biology, University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rattei
authors.affiliation: Scientific Computing Research Unit, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Wolfgang Zu
authors.initials: WZ
authors.lastname: Castell
authors.affiliation: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Martin Hrabé
authors.initials: MH
authors.lastname: de Angelis
authors.affiliation: Research Unit Microbe-Plant Interactions, Research Group Molecular Microbial Ecology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: 1] Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany [2] Technische Universität München, Chair of Analytical Food Chemistry, Freising-Weihenstephan, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Schmitt-Kopplin
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002432:Cecum / Q000378:metabolism / Q000382:microbiology; D059305:Diet, High-Fat; D041981:Gastrointestinal Tract / Q000382:microbiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008810:Mice, Inbred C57BL; D064307:Microbiota; D009765:Obesity / Q000378:metabolism* / Q000382:microbiology*; D053719:Tandem Mass Spectrometry
chemical_list: D001647:Bile Acids and Salts