Antibiotics in early life alter the murine colonic microbiome and adiposity.

Antibiotics in early life alter the murine colonic microbiome and adiposity.
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DOI:
10.1038/nature11400
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发表时间:
2012-08-30
期刊:
影响因子:
64.8
通讯作者:
Blaser, Martin J.
Blaser, Martin J.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cho, Ilseung;Yamanishi, Shingo;Cox, Laura;Methe, Barbara A.;Zavadil, Jiri;Li, Kelvin;Gao, Zhan;Mahana, Douglas;Raju, Kartik;Teitler, Isabel;Li, Huilin;Alekseyenko, Alexander V.;Blaser, Martin J.

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自20世纪50年代以来,低剂量施用的抗生素已被广泛用作农业工业中的生长促进剂,但这种作用的机制尚不清楚。由于不同类别和不同活性的抗微生物剂在几种脊椎动物物种中有效,我们假设这种亚治疗给药改变了肠道微生物组的群体结构及其代谢能力。我们通过对年轻小鼠进行亚治疗抗生素治疗来产生肥胖模型,并评估肠道微生物组的组成和能力的变化。给药亚治疗抗生素治疗增加了幼鼠的肥胖,并增加了与代谢相关的激素。我们观察到微生物组的大量分类变化,参与碳水化合物代谢为短链脂肪酸的关键基因拷贝的变化,结肠短链脂肪酸水平的增加,以及脂质和胆固醇的肝脏代谢调节的改变。在这个模型中,我们证明了通过抗生素操作的早期小鼠代谢稳态的改变。
Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we hypothesized that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormones related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation.
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