Hyperinsulinemia can be a cause and consequence of obesity and insulin resistance. Increased insulin secretion and reduced insulin clearance can contribute to hyperinsulinemia. The triggers for changes in insulin clearance during obesity are ill-defined. We found that oral antibiotics mitigated impaired insulin clearance in mice fed a high fat diet (HFD) for 12 weeks or longer. Short-term HFD feeding and aging did not alter insulin clearance in mice. Germ-free mice colonized with microbes from HFD-fed mice had impaired insulin clearance, but not C-peptide clearance, and only after mice were colonized for 6 weeks and then HFD-fed. Five bacterial taxa predicted >90% of the variance in insulin clearance. Our data indicate that gut microbes are an independent and transmissible factor that regulates obesity-induced changes in insulin clearance. A small cluster of microbes may be a target for mitigating defects in insulin clearance and the progression of obesity and Type 2 Diabetes. We propose that a small community in the gut microbiota can impair insulin clearance and increase insulin load and the risk of complications from hyperinsulinemia.

中文翻译：

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肥胖期间肠道菌群损害胰岛素清除

高胰岛素血症可能是肥胖和胰岛素抵抗的原因和结果。胰岛素分泌增加和胰岛素清除率降低可导致高胰岛素血症。肥胖期间胰岛素清除率变化的触发因素尚不明确。我们发现，口服高脂饮食（HFD）12周或更长时间的小鼠，口服抗生素可减轻受损的胰岛素清除。短期HFD喂养和衰老不会改变小鼠的胰岛素清除率。仅在将小鼠定殖6周后再进行HFD喂养后，用来自HFD喂养的小鼠的微生物定居的无毒小鼠的胰岛素清除率会受损，但C肽清除能力不会受损。五个细菌类群预测胰岛素清除率变异的> 90％。我们的数据表明，肠道微生物是调节肥胖引起的胰岛素清除率变化的独立且可传播的因子。一小群微生物可能是减轻胰岛素清除率以及肥胖症和2型糖尿病进展的目标。我们建议肠道菌群中的一个小社区可以损害胰岛素清除并增加胰岛素负荷以及高胰岛素血症引起并发症的风险。