title: Environmental spread of microbes impacts the development of metabolic phenotypes in mice transplanted with microbial communities from humans.
abstract: Microbiota transplantation to germ-free animals is a powerful method to study involvement of gut microbes in the aetiology of metabolic syndrome. Owing to large interpersonal variability in gut microbiota, studies with broad coverage of donors are needed to elucidate the establishment of human-derived microbiotas in mice, factors affecting this process and resulting impact on metabolic health. We thus transplanted faecal microbiotas from humans (16 obese and 16 controls) separately into 64 germ-free Swiss Webster mice caged in pairs within four isolators, with two isolators assigned to each phenotype, thereby allowing us to explore the extent of microbial spread between cages in a well-controlled environment. Despite high group-wise similarity between obese and control human microbiotas, transplanted mice in the four isolators developed distinct gut bacterial composition and activity, body mass gain, and insulin resistance. Spread of microbes between cages within isolators interacted with establishment of the transplanted microbiotas in mice, and contributed to the transmission of metabolic phenotypes. Our findings highlight the impact of donor variability and reveal that inter-individual spread of microbes contributes to the development of metabolic traits. This is of major importance for design of animal studies, and indicates that environmental transfer of microbes between individuals may affect host metabolic traits.
authors.affiliation: National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Martin Iain
authors.initials: MI
authors.lastname: Bahl
authors.affiliation: National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Henrik Munch
authors.identifier: 0000-0002-2504-8313
authors.initials: HM
authors.lastname: Roager
authors.affiliation: The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Cilius Esmann
authors.identifier: 0000-0002-5031-0125
authors.initials: CE
authors.lastname: Fonvig
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Lars I
authors.initials: LI
authors.lastname: Hellgren
authors.affiliation: National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Henrik Lauritz
authors.initials: HL
authors.lastname: Frandsen
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens-Christian
authors.initials: JC
authors.lastname: Holm
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Tine Rask
authors.identifier: 0000-0002-6399-9574
authors.initials: TR
authors.lastname: Licht
mesh_terms: D000293:Adolescent; D000818:Animals; D016022:Case-Control Studies; D002648:Child; D000069467:Fecal Microbiota Transplantation; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D005856:Germ-Free Life; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D009765:Obesity / Q000097:blood / Q000382:microbiology*
chemical_list: D008055:Lipids