Environmental spread of microbes impact the development of metabolic phenotypes in mice transplanted with microbial communities from humans

Gut microbiota transplantation to germ-free (GF) animals is a powerful method to study the involvement of gut microbes in the aetiology of the metabolic syndrome. Due to the 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 consequent impact on metabolic health of the host. We thus transplanted faecal microbiotas from human donors (16 obese and 16 control) separately into 64 GF Swiss Webster mice caged in pairs and housed in four isolators, with two isolators assigned to each phenotype. Despite high similarity between obese and control donor microbiotas, transplanted mice in the four isolators developed distinct gut bacterial composition and activity, body mass gain and insulin resistance. Environmental spread of microbes within each isolator interacted with establishment of the human microbiotas in mice, and, importantly, contributed to the transmission of specific 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 great importance for design of animal studies, and indicates that environmental transfer of microbes between individuals may affect host metabolic traits.