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

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, Eliana Mariño, Rob J. Moore, Lee Wong, Malcolm J. McConville, Dedreia L. Tull, Lisa G. Wood, Vanessa E. Murphy, Joerg Mattes, Peter G. Gibson and Charles R. Mackay ()
Additional contact information
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
Jian K. Tan: Monash University
Eliana Mariño: Monash University
Rob J. Moore: CSIRO Animal, Food, and Health Sciences, Geelong, Victoria 3220, Australia
Lee Wong: Monash University
Malcolm J. McConville: Bio21 Institute of Molecular Science 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

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8320

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