Cultured gut bacterial consortia from twins discordant for obesity modulate adiposity in gnotobiotic mice

Efforts to characterize the human microbiome are producing large amounts of data about its organismal and gene content. A challenge is to complement these efforts with a preclinical research pipeline that directly tests the degree to which a person's physiologic or pathological phenotype relates to their microbiome. We illustrate such a 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 mice fed a low-fat, plant polysaccharide-rich diet. Capture of a human donor's microbiota in recipient mice is highly reproducible. The increased adiposity phenotype of obese co-twins is transmissible not only with the uncultured fecal communities, but with bacterial culture collections generated from these fecal samples. Co-housing mice colonized with a culture collection produced from an obese co-twin's microbiota (Ob), with mice harboring the culturable component of the lean co-twin's microbiota (Ln) prevented development of an increased adiposity phenotype in Ob animals. These results correlate with invasion of specific members from the culturable component of the Ln co-twin's microbiota into the guts of Ob cagemates, and transformation of the Ob microbiota's metabolic profile to a lean-like state.