Journal article
Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites
AN Thorburn, CI McKenzie, S Shen, D Stanley, L MacIa, LJ Mason, LK Roberts, CHY Wong, R Shim, R Robert, N Chevalier, JK Tan, E Marinõ, RJ Moore, L Wong, MJ McConville, DL Tull, LG Wood, VE Murphy, J Mattes Show all
Nature Communications | Published : 2015
DOI: 10.1038/ncomms8320
Open access
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 thei..
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Funding Acknowledgements
We thank Monash animal facilities, Histology Platform and FlowCore. We acknowledge Vicki Clifton, Philippa Talbot, Kelly Steel, Penelope McLernon and Karen McLaughlin for human sample and data collection, Phillipe Collas for assistance with ChIP, Andreas Suhrbier for IPA, Magdalena Hubalewska and Marcin Surmiak for qPCR and western blot, Ashlee Burt and Laurent Juglair for general assistance and Pat Holt for critically reviewing this manuscript. Jason Bell provided High Performance Computing support. This work was supported by NHMRC, CRC for Asthma and airways, The University of Newcastle, Asthma Foundation NSW, HMRI, Port Waratah Coal Services and Hunter Children's Research Foundation.