title: High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice.
abstract: It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity.
  
  
  
  Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF or a HF diet. Conversely, the abundance of genes involved in propionate metabolism, associated with increased energy harvest, was higher in BL6 mice than Sv129 mice.
  
  
  
  The changes in the composition of the gut microbiota were predominantly driven by high-fat feeding rather than reflecting the obese state of the mice. Differences in the abundance of butyrate and propionate producing bacteria in the gut may at least in part contribute to the observed differences in obesity propensity in Sv129 and BL6 mice.
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark.
authors.forename: Si Brask
authors.initials: SB
authors.lastname: Sonne
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.|Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Zhongkui
authors.initials: Z
authors.lastname: Xia
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Fang
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Dongya
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark.|National Institute of Nutrition and Seafood Research (NIFES), Postboks 2029, Nordnes, N-5817, Bergen, Norway.
authors.forename: Even
authors.initials: E
authors.lastname: Fjære
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark.|National Institute of Nutrition and Seafood Research (NIFES), Postboks 2029, Nordnes, N-5817, Bergen, Norway.
authors.forename: Lisa Kolden
authors.initials: LK
authors.lastname: Midtbø
authors.affiliation: Laboratory of Microbiology, Wageningen University, 6701 AK, Wageningen, The Netherlands.|Present address: Danone Research, TI Food and Nutrition, Paris, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Derrien
authors.affiliation: Laboratory of Microbiology, Wageningen University, 6701 AK, Wageningen, The Netherlands.
authors.forename: Floor
authors.initials: F
authors.lastname: Hugenholtz
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Longqing
authors.initials: L
authors.lastname: Tang
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hao
authors.affiliation: National Research Centre for the Working Environment, DK-2100, Copenhagen, Denmark.
authors.forename: Ulla Birgitte
authors.initials: UB
authors.lastname: Vogel
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark.
authors.forename: Alicja
authors.initials: A
authors.lastname: Mortensen
authors.affiliation: Laboratory of Microbiology, Wageningen University, 6701 AK, Wageningen, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Kleerebezem
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark.
authors.forename: Tine Rask
authors.initials: TR
authors.lastname: Licht
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.|James D. Watson Institute of Genome Sciences, Hangzhou, 310058, China.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.|James D. Watson Institute of Genome Sciences, Hangzhou, 310058, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.|The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DK-2100, Denmark.
authors.forename: Manimozhiyan
authors.initials: M
authors.lastname: Arumugam
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.|Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.|Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark.|National Institute of Nutrition and Seafood Research (NIFES), Postboks 2029, Nordnes, N-5817, Bergen, Norway.
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China. kk@bio.ku.dk.|Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark. kk@bio.ku.dk.
authors.forename: Karsten
authors.identifier: 0000-0002-6024-0917
authors.initials: K
authors.lastname: Kristiansen
mesh_terms: D000818:Animals; D041963:Bacteroidetes / Q000254:growth & development / Q000302:isolation & purification; D002087:Butyrates / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000378:metabolism*; D000068536:Bacillota / Q000254:growth & development / Q000302:isolation & purification; D000069196:Gastrointestinal Microbiome; D016680:Genome, Bacterial / Q000235:genetics; D007213:Indomethacin / Q000494:pharmacology; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity; D011422:Propionates / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
chemical_list: D002087:Butyrates; D016861:Cyclooxygenase Inhibitors; D004041:Dietary Fats; D011422:Propionates; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin
keywords: 129S6/Sv mice; C57BL/6J mice; High-fat feeding; Indomethacin; Microbiome; Microbiota; Obesity