characterizing the gut communitties of twins discordant for obesity in gnotobiotic mice

International efforts to characterize the human microbiome in health and disease are producing massive amounts of data about organismal and gene content in our body habitat -associated microbial communities. A challenge is to complement these efforts with a preclinical research pipeline that tests the degree to which a person's physiologic or pathological phenotype can be ascribed to their microbiome and that offers an opportunity to evaluate potential strategies for microbiome-based therapeutics. Here we illustrate such a pre-clinical pipeline by transplanting previously frozen, uncultured fecal microbiota samples from four sets of adult female mono- and dizygotic twins discordant for obesity into groups of adult germ-free C57Bl/6J mice fed a low-fat, plant polysaccharide-rich diet. Capture of a human donor's microbiota in recipient mice is highly reproducible within and between experiments. The increased adiposity phenotype of obese co-twins is transmissible not only with the intact uncultured fecal communities, but with bacterial culture collections generated from these fecal samples. Co-housing mice five days after they received transplants of culture collections from the obese or lean member of a discordant twin pair ameliorated the increased adiposity phenotype that normally develops in recipients of the obese donor's culture collection, while having no effect on the adiposity phenotype of recipients of the lean co-twin's culture collection. These results correlate with taxonomic and metabolic changes in co-housed mice harboring the obese co-twin's culture collection. Our results demonstrate a way to perform pre-clinical studies of microbiome-associated human phenotypes, including methods for identifying, producing and testing candidate probiotic species as therapeutic or preventative agents.