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

Alison N Thorburn, Craig McKenzie, Sj S 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 M Marino, Robert J Moore, Lee Hwa Hwa Wong, Malcolm J McConville, Dedreia L Tull, Lisa Wood, Vanessa Murphy, Joerg Mattes & 3 others Peter G Gibson, Lisa G Wood, Charles R Mackay

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237 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1 - 13
Number of pages13
JournalNature Communications
Volume6
Issue number7320
DOIs
Publication statusPublished - 2015

Cite this

Thorburn, Alison N ; McKenzie, Craig ; Shen, Sj S ; Stanley, Dragana ; Macia, Laurence ; Mason, Linda J ; Roberts, Laura K ; Wong, Connie H Y ; Shim, Raymond ; Robert, Remy ; Chevalier, Nina ; Tan, Jian K ; Marino, Eliana M ; Moore, Robert J ; Wong, Lee Hwa Hwa ; McConville, Malcolm J ; Tull, Dedreia L ; Wood, Lisa ; Murphy, Vanessa ; Mattes, Joerg ; Gibson, Peter G ; Wood, Lisa G ; Mackay, Charles R. / Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites. In: Nature Communications. 2015 ; Vol. 6, No. 7320. pp. 1 - 13.
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title = "Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites",
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.",
author = "Thorburn, {Alison N} and Craig McKenzie and Shen, {Sj S} and Dragana Stanley and Laurence Macia and Mason, {Linda J} and Roberts, {Laura K} and Wong, {Connie H Y} and Raymond Shim and Remy Robert and Nina Chevalier and Tan, {Jian K} and Marino, {Eliana M} and Moore, {Robert J} and Wong, {Lee Hwa Hwa} and McConville, {Malcolm J} and Tull, {Dedreia L} and Lisa Wood and Vanessa Murphy and Joerg Mattes and Gibson, {Peter G} and Wood, {Lisa G} and Mackay, {Charles R}",
year = "2015",
doi = "10.1038/ncomms8320",
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Thorburn, AN, McKenzie, C, Shen, SS, Stanley, D, Macia, L, Mason, LJ, Roberts, LK, Wong, CHY, Shim, R, Robert, R, Chevalier, N, Tan, JK, Marino, EM, Moore, RJ, Wong, LHH, McConville, MJ, Tull, DL, Wood, L, Murphy, V, Mattes, J, Gibson, PG, Wood, LG & Mackay, CR 2015, 'Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites', Nature Communications, vol. 6, no. 7320, pp. 1 - 13. https://doi.org/10.1038/ncomms8320

Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites. / Thorburn, Alison N; McKenzie, Craig; Shen, Sj S; Stanley, Dragana; Macia, Laurence; Mason, Linda J; Roberts, Laura K; Wong, Connie H Y; Shim, Raymond; Robert, Remy; Chevalier, Nina; Tan, Jian K; Marino, Eliana M; Moore, Robert J; Wong, Lee Hwa Hwa; McConville, Malcolm J; Tull, Dedreia L; Wood, Lisa; Murphy, Vanessa; Mattes, Joerg; Gibson, Peter G; Wood, Lisa G; Mackay, Charles R.

In: Nature Communications, Vol. 6, No. 7320, 2015, p. 1 - 13.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites

AU - Thorburn, Alison N

AU - McKenzie, Craig

AU - Shen, Sj S

AU - Stanley, Dragana

AU - Macia, Laurence

AU - Mason, Linda J

AU - Roberts, Laura K

AU - Wong, Connie H Y

AU - Shim, Raymond

AU - Robert, Remy

AU - Chevalier, Nina

AU - Tan, Jian K

AU - Marino, Eliana M

AU - Moore, Robert J

AU - Wong, Lee Hwa Hwa

AU - McConville, Malcolm J

AU - Tull, Dedreia L

AU - Wood, Lisa

AU - Murphy, Vanessa

AU - Mattes, Joerg

AU - Gibson, Peter G

AU - Wood, Lisa G

AU - Mackay, Charles R

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pubmed/26102221

U2 - 10.1038/ncomms8320

DO - 10.1038/ncomms8320

M3 - Article

VL - 6

SP - 1

EP - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 7320

ER -