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.

肥胖及其后果是医疗保健领域面临的最大挑战之一。肠道微生物组被认为是肥胖发病机制的关键因素。我们使用小鼠模型在此展示，在为期 10 周的高脂肪饮食过程中，野生来源的微生物组可以防止体重过度增加、严重的脂肪肝疾病和代谢综合征。这种表型只能在生命的最初几周转移。在成年小鼠中，野生型微生物组的转移或严重干扰都不会改变对高脂肪饮食的代谢反应。保护性表型与代谢激素分泌增加和通过激活棕色脂肪组织增加能量消耗有关。因此，我们确定了一种微生物组，该微生物组可通过生命早期的代谢编程来防止体重增加及其负面影响。将这些结果转化为人类可能会发现预防肥胖的早期治疗方法。