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

被引：707

作者：

Thorburn, Alison N. ^{[1
]}

McKenzie, Craig I. ^{[1
]}

Shen, Sj ^{[1
]}

Stanley, Dragana ^{[2
]}

Macia, Laurence ^{[1
]}

Mason, Linda J. ^{[1
]}

Roberts, Laura K. ^{[1
]}

Wong, Connie H. Y. ^{[1
]}

Shim, Raymond ^{[1
]}

Robert, Remy ^{[1
]}

Chevalier, Nina ^{[1
,3
]}

Tan, Jian K. ^{[1
]}

Marino, Eliana ^{[1
]}

Moore, Rob J. ^{[4
,5
]}

Wong, Lee ^{[6
]}

McConville, Malcolm J. ^{[7
,8
]}

Tull, Dedreia L. ^{[8
]}

Wood, Lisa G. ^{[9
]}

Murphy, Vanessa E. ^{[9
]}

Mattes, Joerg ^{[9
]}

Gibson, Peter G. ^{[9
]}

Mackay, Charles R. ^{[1
,10
]}

机构：

[1] Monash Univ, Dept Immunol, Clayton, Vic 3800, Australia

[2] Cent Queensland Univ, Sch Med & Appl Sci, Rockhampton, Qld 4072, Australia

[3] Univ Med Ctr, Dept Rheumatol & Clin Immunol, D-79106 Freiburg, Germany

[4] CSIRO, Anim Food & Hlth Sci, Geelong, Vic 3220, Australia

[5] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia

[6] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

[7] Univ Melbourne, Inst Mol Sci & Biotechnol Bio21, Dept Biochem & Mol Biol, Melbourne, Vic 3010, Australia

[8] Univ Melbourne, Inst Mol Sci & Biotechnol Bio21, Metabol Australia, Melbourne, Vic 3010, Australia

[9] Univ Newcastle, Hunter Med Res Inst, Ctr Asthma & Resp Dis, Newcastle, NSW 2300, Australia

[10] Univ Sydney, Sch Med, Charles Perkins Ctr, Sydney, NSW 2006, Australia

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

REGULATORY T-CELLS; ALLERGIC AIRWAYS DISEASE; GUT MICROBIOTA; RESPIRATORY SYMPTOMS; PREGNANT-WOMEN; LIFE-STYLE; FAST FOODS; INFLAMMATION; EXPRESSION; RECEPTOR;

D O I：

10.1038/ncomms8320

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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