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.

Consistent alterations of human fecal microbes after transplanted to germ-free mice

“…As shown in Figure 1, we estimated that on average only 47% human gut microbes could be re-established in mouse gut at species level after FMT; at genus level, ~60% could re-established. These numbers are consistent with some previous results [29] but differ significantly from others [30, 31]. For example, using 64 human-mouse pairs, Ridaura et al estimated 50~90% of human gut microbes at genus level could be re-established in mice after FMT, while others have found slightly higher re-establishment rates (>85% [30, 31]).…”

Mechanisms Preserving Insulin Action during High Dietary Fat Intake

“…Even though multiple KEGG modules showed organism-specific changes, 19 of the 23 modules affected by the PUFA diet in both humans and mice exhibited a similar pattern ( Figure 5C). Thus, despite different microbiome taxonomical compositions, which is to be expected comparing mice and humans (Zhang et al, 2017), the functional capacity of the microbiome exhibited similar responses to the PUFA diet, with one of the most notable uniform changes being increased capacity for glycerol degradation. The modules that were altered in opposite direction between humans and mice most probably reflect differences between the human habitual diets and the less complex low-fat diet fed to the mice.…”

Gut microbiome interventions in human health and diseases

“…Human diseases are often the result of intricate interactions between genetic and environmental factors, and studying the effects of gut microbiota in such a complex organism is affected by multiple factors. Because of the striking differences between microbiota profiles in humans and mice, especially in more detailed taxonomic units, transplanting microbes from human feces into the intestines of sterile mice to transform them into so‐called humanized mice sheds light on the function of the human gut microbiota, but researchers have still failed to establish a subset of human‐derived gut microbes . Furthermore, methods for identifying intestinal microbiota components are inconsistent among studies, with additional difficulty regarding comparison and reference.…”

“…Environmental interventions, probiotic supplementation, fecal transplantation, and nonantibiotic drugs can be used to restore gut microbiota homeostasis for disease prevention and improvement detailed taxonomic units, transplanting microbes from human feces into the intestines of sterile mice to transform them into so-called humanized mice sheds light on the function of the human gut microbiota, but researchers have still failed to establish a subset of human-derived gut microbes. 151,253,254 Furthermore, methods for identifying intestinal microbiota components are inconsistent among studies, with additional difficulty regarding comparison and reference. Dubilier et al 20 have called on global scientists to work for an International Microbiome Initiative such that researchers can share standard methods for experimental design and data analysis.…”