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Obesity and its consequences are among the greatest challenges in healthcare. The gut microbiome is recognized as a key factor in the pathogenesis of obesity. Using a mouse model, we show here that a wild-derived microbiome protects against excessive weight gain, severe fatty liver disease and metabolic syndrome during a 10-week course of high-fat diet. This phenotype is transferable only during the first weeks of life. In adult mice, neither transfer nor severe disturbance of the wild-type microbiome modifies the metabolic response to a high-fat diet. The protective phenotype is associated with increased secretion of metabolic hormones and increased energy expenditure through activation of brown adipose tissue. Thus, we identify a microbiome that protects against weight gain and its negative consequences through metabolic programming in early life. Translation of these results to humans may identify early-life therapeutics that protect against obesity.
Benedikt Hild,Matthew S Dreier,Ji Hoon Oh,John A McCulloch,Jonathan H Badger,Juen Guo,Claire E Thefaine,Regina Umarova,Kevin D Hall,Oksana Gavrilova,Stephan P Rosshart,Giorgio Trinchieri,Barbara Rehermann