Environmental spread of microbes impacts the development of metabolic phenotypes in mice transplanted with microbial communities from humans
Li Zhang1, Martin Iain Bahl1, Henrik Munch Roager1, Cilius Esmann Fonvig2,3, Lars I Hellgren4, Henrik Lauritz Frandsen1, Oluf Pedersen3, Jens-Christian Holm2,3, Torben Hansen3 and Tine Rask Licht1
1National Food Institute, Technical University of Denmark, Søborg, Denmark
2The Children’s Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark
3Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
4Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark
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.
ISME Journal doi: 10.1038/ismej.2016.151