Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

被引:291
作者
Nobel, Yael R. [1 ]
Cox, Laura M. [1 ,2 ]
Kirigin, Francis F. [1 ]
Bokulich, Nicholas A. [1 ]
Yamanishi, Shingo [1 ]
Teitler, Isabel [1 ]
Chung, Jennifer [1 ]
Sohn, Jiho [1 ]
Barber, Cecily M. [1 ]
Goldfarb, David S. [1 ,3 ]
Raju, Kartik [1 ]
Abubucker, Sahar [4 ]
Zhou, Yanjiao [4 ,5 ,9 ]
Ruiz, Victoria E. [1 ]
Li, Huilin [6 ]
Mitreva, Makedonka [4 ,7 ]
Alekseyenko, Alexander V. [1 ,8 ]
Weinstock, George M. [4 ,9 ]
Sodergren, Erica [4 ,9 ]
Blaser, Martin J. [1 ,2 ,3 ]
机构
[1] NYU, Sch Med, Dept Med, New York, NY 10016 USA
[2] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA
[3] New York Harbor Dept Vet Affairs Med Ctr, New York, NY 10010 USA
[4] Washington Univ, Genome Inst, St Louis, MO 63108 USA
[5] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
[6] NYU, Langone Med Ctr, Dept Populat Hlth, Div Biostat, New York, NY 10016 USA
[7] Washington Univ, Sch Med, Dept Internal Med, Div Infect Dis, St Louis, MO 63110 USA
[8] NYU, Sch Med, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA
[9] Jackson Lab Genom Med, Farmington, CT 06117 USA
关键词
GUT MICROBIOTA; CHILDHOOD OVERWEIGHT; AMOXICILLIN; PHARMACOKINETICS; COLONIZATION; ENVIRONMENT; ASSOCIATION; ALIGNMENT; EXPOSURE; WEIGHT;
D O I
10.1038/ncomms8486
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
Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.
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页数:15
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