Antibiotics in early life alter the murine colonic microbiome and adiposity

被引:1230
作者
Cho, Ilseung [1 ,2 ]
Yamanishi, Shingo [1 ]
Cox, Laura [3 ]
Methe, Barbara A. [4 ]
Zavadil, Jiri [5 ,6 ]
Li, Kelvin [4 ]
Gao, Zhan [3 ]
Mahana, Douglas [3 ]
Raju, Kartik [3 ]
Teitler, Isabel [3 ]
Li, Huilin [7 ]
Alekseyenko, Alexander V. [1 ,6 ]
Blaser, Martin J. [1 ,2 ,3 ]
机构
[1] NYU, Sch Med, Dept Med, New York, NY 10016 USA
[2] VA New York Harbor Healthcare Syst, Med Serv, New York, NY 10010 USA
[3] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA
[4] J Craig Venter Inst, Rockville, MD 20850 USA
[5] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA
[6] NYU, Sch Med, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA
[7] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA
关键词
GASTRIC-INHIBITORY POLYPEPTIDE; CHAIN FATTY-ACIDS; RECEPTOR KNOCKOUT MICE; DIET-INDUCED OBESITY; GUT MICROBIOME; INTESTINAL MICROBIOTA; COMMUNITIES; DIVERSITY; SEQUENCES; DISEASE;
D O I
10.1038/nature11400
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 proposed 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 hormone levels 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.
引用
收藏
页码:621 / +
页数:9
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