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Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites

Author

Listed:
  • Alison N. Thorburn

    (Monash University)

  • Craig I. McKenzie

    (Monash University)

  • Sj Shen

    (Monash University)

  • Dragana Stanley

    (School of Medical and Applied Sciences, Central Queensland University)

  • Laurence Macia

    (Monash University)

  • Linda J. Mason

    (Monash University)

  • Laura K. Roberts

    (Monash University)

  • Connie H. Y. Wong

    (Monash University)

  • Raymond Shim

    (Monash University)

  • Remy Robert

    (Monash University)

  • Nina Chevalier

    (Monash University
    University Medical Center)

  • Jian K. Tan

    (Monash University)

  • Eliana Mariño

    (Monash University)

  • Rob J. Moore

    (CSIRO Animal, Food, and Health Sciences, Geelong, Victoria 3220, Australia
    Monash University)

  • Lee Wong

    (Monash University)

  • Malcolm J. McConville

    (Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne
    Metabolomics Australia, Bio21 Institute of Molecular Sciences and Biotechnology, University of Melbourne)

  • Dedreia L. Tull

    (Metabolomics Australia, Bio21 Institute of Molecular Sciences and Biotechnology, University of Melbourne)

  • Lisa G. Wood

    (Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle)

  • Vanessa E. Murphy

    (Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle)

  • Joerg Mattes

    (Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle)

  • Peter G. Gibson

    (Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle)

  • Charles R. Mackay

    (Monash University
    Charles Perkins Centre, Sydney University Medical School, University of Sydney)

Abstract

Asthma is prevalent in Western countries, and recent explanations have evoked the actions of the gut microbiota. Here we show that feeding mice a high-fibre diet yields a distinctive gut microbiota, which increases the levels of the short-chain fatty acid, acetate. High-fibre or acetate-feeding led to marked suppression of allergic airways disease (AAD, a model for human asthma), by enhancing T-regulatory cell numbers and function. Acetate increases acetylation at the Foxp3 promoter, likely through HDAC9 inhibition. Epigenetic effects of fibre/acetate in adult mice led us to examine the influence of maternal intake of fibre/acetate. High-fibre/acetate feeding of pregnant mice imparts on their adult offspring an inability to develop robust AAD. High fibre/acetate suppresses expression of certain genes in the mouse fetal lung linked to both human asthma and mouse AAD. Thus, diet acting on the gut microbiota profoundly influences airway responses, and may represent an approach to prevent asthma, including during pregnancy.

Suggested Citation

  • Alison N. Thorburn & Craig I. McKenzie & Sj Shen & Dragana Stanley & Laurence Macia & Linda J. Mason & Laura K. Roberts & Connie H. Y. Wong & Raymond Shim & Remy Robert & Nina Chevalier & Jian K. Tan , 2015. "Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8320
    DOI: 10.1038/ncomms8320
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