Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

Yael R. Nobel; Laura M. Cox; Francis F. Kirigin; Nicholas A. Bokulich; Shingo Yamanishi; Isabel Teitler; Jennifer Chung; Jiho Sohn; Cecily M. Barber; David S. Goldfarb; Kartik Raju; Sahar Abubucker; Yanjiao Zhou; Victoria E. Ruiz; Huilin Li; Makedonka Mitreva; Alexander V. Alekseyenko; George M. Weinstock; Erica Sodergren; Martin J. Blaser

doi:10.1038/ncomms8486

Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

Yael R. Nobel, Laura M. Cox, Francis F. Kirigin, Nicholas A. Bokulich, Shingo Yamanishi, Isabel Teitler, Jennifer Chung, Jiho Sohn, Cecily M. Barber, David S. Goldfarb, Kartik Raju, Sahar Abubucker, Yanjiao Zhou, Victoria E. Ruiz, Huilin Li, Makedonka Mitreva, Alexander V. Alekseyenko, George M. Weinstock, Erica Sodergren, Martin J. Blaser

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Abstract

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.

Original language	English
Article number	7486
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8486
State	Published - Jun 30 2015

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Nobel, Y. R., Cox, L. M., Kirigin, F. F., Bokulich, N. A., Yamanishi, S., Teitler, I., Chung, J., Sohn, J., Barber, C. M., Goldfarb, D. S., Raju, K., Abubucker, S., Zhou, Y., Ruiz, V. E., Li, H., Mitreva, M., Alekseyenko, A. V., Weinstock, G. M., Sodergren, E., & Blaser, M. J. (2015). Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment. Nature communications, 6, Article 7486. https://doi.org/10.1038/ncomms8486

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title = "Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment",

abstract = "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.",

author = "Nobel, {Yael R.} and Cox, {Laura M.} and Kirigin, {Francis F.} and Bokulich, {Nicholas A.} and Shingo Yamanishi and Isabel Teitler and Jennifer Chung and Jiho Sohn and Barber, {Cecily M.} and Goldfarb, {David S.} and Kartik Raju and Sahar Abubucker and Yanjiao Zhou and Ruiz, {Victoria E.} and Huilin Li and Makedonka Mitreva and Alekseyenko, {Alexander V.} and Weinstock, {George M.} and Erica Sodergren and Blaser, {Martin J.}",

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Nobel, YR, Cox, LM, Kirigin, FF, Bokulich, NA, Yamanishi, S, Teitler, I, Chung, J, Sohn, J, Barber, CM, Goldfarb, DS, Raju, K, Abubucker, S, Zhou, Y, Ruiz, VE, Li, H, Mitreva, M, Alekseyenko, AV, Weinstock, GM, Sodergren, E & Blaser, MJ 2015, 'Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment', Nature communications, vol. 6, 7486. https://doi.org/10.1038/ncomms8486

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AU - Bokulich, Nicholas A.

AU - Yamanishi, Shingo

AU - Teitler, Isabel

AU - Chung, Jennifer

AU - Sohn, Jiho

AU - Barber, Cecily M.

AU - Goldfarb, David S.

AU - Raju, Kartik

AU - Abubucker, Sahar

AU - Zhou, Yanjiao

AU - Ruiz, Victoria E.

AU - Li, Huilin

AU - Mitreva, Makedonka

AU - Alekseyenko, Alexander V.

AU - Weinstock, George M.

AU - Sodergren, Erica

AU - Blaser, Martin J.

PY - 2015/6/30

Y1 - 2015/6/30

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AB - 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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Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

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