Human microbiota mouse models are an attractive, translational tool to evaluate the role of the intestinal microbiota in the pathology of obesity. However, germ-free mice lack translational value due to a lack of microbiota to foster complete host development. We hypothesized that, following antibiotic conditioning, a human microbiota could be successfully engrafted in conventionally housed mice to study its role in developing an obese host phenotype.
Donor fecal material from each of two obese or lean donors was given to mice (males & females) by a single oral gavage following antibiotic conditioning. Control mice that did not receive donor material were also included. Mice were fed normal chow, and weights were monitored over a 12-week follow-up. Microbiota composition was characterized by Illumina amplicon sequencing and insulin sensitivity and glucose tolerance were also tested.
Mice that received obese donor material gained more weight than those given lean donor material, independent of sex (ANOVA P ≤ 0.001). Furthermore, mice that received the obese donor material also showed disrupted glucose homeostasis, with obese male mice showing greater resistance to insulin (P = 0.033), while obese female mice showed decreased glucose tolerance (P = 0.013), relative to mice who received lean donor material. Significant differences were also observed in microbial community composition between obese and lean mice (ANOSIM R = 0.32, P < 0.001). Bacterial communities in lean mice were comprised of significantly greater relative abundances of Bacteroides, while obese mice had greater abundances of Enterobacter.
The microbiota alone play a significant role in the progression of obesity and disrupted glucose homeostasis and may be a modifiable target for the management or treatment of obesity. Moreover, this model provides an accessible and translational model to mechanistically characterize the role of the intestinal microbiota in obesity, outside of a germ-free facility.