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Antibiotics in early life alter the murine colonic microbiome and adiposity

Nature volume 488, pages 621–626 (2012)Cite this article

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Abstract

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.

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Figure 1: Weight and body composition of control and STAT mice.
Figure 2: Bone development and serum GIP measurements.
Figure 3: Changes in the faecal gut microbiome after 50 days of STAT.
Figure 4: Caecal SCFA production after STAT exposure.
Figure 5: Differentially regulated genes related to hepatic lipogenesis, identified through microarray and quantitative PCR analyses.

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Acknowledgements

This work was supported in part with grants from the NIH (T-RO1-DK090989, 1UL1-RR029893, UL1-TR000038), the Diane Belfer Program in Human Microbial Ecology, the Philip and Janice Levin Foundation, the Michael Saperstein Fellowship, and institutional funds provided by the J. Craig Venter Institute, and the NYU Genome Technology Center. We thank N. Javitt for advice and J. Chung for technical assistance.

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Authors and Affiliations

  1. Department of Medicine, New York University School of Medicine, New York, 10016, New York, USA

    Ilseung Cho, Shingo Yamanishi, Alexander V. Alekseyenko & Martin J. Blaser

  2. Medical Service, VA New York Harbor Healthcare System, New York, 10010, New York, USA

    Ilseung Cho & Martin J. Blaser

  3. Department of Microbiology, New York University School of Medicine, New York, 10016, New York, USA

    Laura Cox, Zhan Gao, Douglas Mahana, Kartik Raju, Isabel Teitler & Martin J. Blaser

  4. J. Craig Venter Institute, Rockville, Maryland, 20850, USA

    Barbara A. Methé & Kelvin Li

  5. Department of Pathology, New York University School of Medicine, New York, 10016, New York, USA

    Jiri Zavadil

  6. Center for Health Informatics and Bioinformatics, New York University School of Medicine, New York, New York, 10016, USA

    Jiri Zavadil & Alexander V. Alekseyenko

  7. Department of Population Health, New York University School of Medicine, New York, New York, 10016, USA

    Huilin Li

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Contributions

I.C. and M.J.B. designed the study; I.C., L.C., S.Y., Z.G., D.M., I.T. and K.R. performed experiments; B.A.M. and K.L. performed sequencing and sequencing analysis; J.Z. performed microarray analyses; I.C. and H.L. performed statistical interpretation and analyses; A.V.A. performed bioinformatics analyses and interpretation; I.C. and M.J.B. took primary responsibility for writing the manuscript.

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Correspondence to Martin J. Blaser.

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Cho, I., Yamanishi, S., Cox, L. et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488, 621–626 (2012). https://doi.org/10.1038/nature11400

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