Ridaura_Cohousing_Humanized_mice_RNAseq

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. Increased adiposity and obesity-associated metabolic phenotypes are 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, mainly Bacteroides spp, into the guts of Ob cagemates, and transformation of the Ob microbiota???s metabolic profile to a lean-like state. To define interrelationships between diet, donor microbiota and host phenotypes, mice were fed a human diet based on USA food consumption patterns. Significantly increased adipose and lean body mass occurred in Ob animals. These phenotypes were rescued by co-housing, accompanied by invasion by Bacteroides spp from Ln cagemates. Together, our findings disclose transmissible, rapid, pronounced and preventable effects of diet-by-microbiota interactions in shaping body composition and metabolism.