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; Charles R Mackay

doi:10.1038/ncomms8320

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

Nat Commun. 2015 Jun 23:6:7320. doi: 10.1038/ncomms8320.

Authors

Alison N Thorburn¹, Craig I McKenzie¹, Sj Shen¹, Dragana Stanley², Laurence Macia¹, Linda J Mason¹, Laura K Roberts¹, Connie H Y Wong¹, Raymond Shim¹, Remy Robert¹, Nina Chevalier³, Jian K Tan¹, Eliana Mariño¹, Rob J Moore⁴, Lee Wong⁵, Malcolm J McConville⁶, Dedreia L Tull⁷, Lisa G Wood⁸, Vanessa E Murphy⁸, Joerg Mattes⁸, Peter G Gibson⁸, Charles R Mackay⁹

Affiliations

¹ Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
² School of Medical and Applied Sciences, Central Queensland University, Rockhampton, Queensland 4702, Australia.
³ 1] Department of Immunology, Monash University, Clayton, Victoria 3800, Australia [2] Department of Rheumatology and Clinical Immunology, University Medical Center, 79106 Freiburg, Germany.
⁴ 1] CSIRO Animal, Food, and Health Sciences, Geelong, Victoria 3220, Australia [2] Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.
⁵ Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
⁶ 1] Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Melbourne, Victoria 3010, Australia [2] Metabolomics Australia, Bio21 Institute of Molecular Sciences and Biotechnology, University of Melbourne, Melbourne, Victoria 3010, Australia.
⁷ Metabolomics Australia, Bio21 Institute of Molecular Sciences and Biotechnology, University of Melbourne, Melbourne, Victoria 3010, Australia.
⁸ Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales 2300, Australia.
⁹ 1] Department of Immunology, Monash University, Clayton, Victoria 3800, Australia [2] Charles Perkins Centre, Sydney University Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.

PMID: 26102221
DOI: 10.1038/ncomms8320

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetates / metabolism*
Acetates / pharmacology
Acetylation / drug effects
Animals
Asthma / immunology
Asthma / metabolism*
Diet*
Dietary Fiber / metabolism*
Disease Models, Animal
Epigenesis, Genetic / drug effects
Fatty Acids, Volatile / metabolism
Fatty Acids, Volatile / pharmacology
Female
Forkhead Transcription Factors / drug effects
Forkhead Transcription Factors / genetics
Gastrointestinal Microbiome*
Histone Deacetylases / drug effects
Histone Deacetylases / metabolism
Mice
Pregnancy
Prenatal Exposure Delayed Effects / immunology
Prenatal Exposure Delayed Effects / metabolism*
Promoter Regions, Genetic
Repressor Proteins / drug effects
Repressor Proteins / metabolism
T-Lymphocytes, Regulatory / cytology
T-Lymphocytes, Regulatory / drug effects
T-Lymphocytes, Regulatory / immunology*

Substances

Acetates
Dietary Fiber
Fatty Acids, Volatile
Forkhead Transcription Factors
Foxp3 protein, mouse
Repressor Proteins
Hdac9 protein, mouse
Histone Deacetylases