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.
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Alison N
authors.initials: AN
authors.lastname: Thorburn
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Craig I
authors.initials: CI
authors.lastname: McKenzie
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Sj
authors.identifier: 0000000210041936
authors.initials: S
authors.lastname: Shen
authors.affiliation: School of Medical and Applied Sciences, Central Queensland University, Rockhampton, Queensland 4702, Australia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Stanley
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Laurence
authors.initials: L
authors.lastname: Macia
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Mason
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Roberts
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Connie H Y
authors.initials: CH
authors.lastname: Wong
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Raymond
authors.initials: R
authors.lastname: Shim
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Remy
authors.initials: R
authors.lastname: Robert
authors.affiliation: 1] Department of Immunology, Monash University, Clayton, Victoria 3800, Australia [2] Department of Rheumatology and Clinical Immunology, University Medical Center, 79106 Freiburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Chevalier
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Jian K
authors.initials: JK
authors.lastname: Tan
authors.affiliation: Department of Immunology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Eliana
authors.initials: E
authors.lastname: Mariño
authors.affiliation: 1] CSIRO Animal, Food, and Health Sciences, Geelong, Victoria 3220, Australia [2] Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Moore
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Lee
authors.initials: L
authors.lastname: Wong
authors.affiliation: 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.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: McConville
authors.affiliation: Metabolomics Australia, Bio21 Institute of Molecular Sciences and Biotechnology, University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: Dedreia L
authors.initials: DL
authors.lastname: Tull
authors.affiliation: Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales 2300, Australia.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Wood
authors.affiliation: Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales 2300, Australia.
authors.forename: Vanessa E
authors.initials: VE
authors.lastname: Murphy
authors.affiliation: Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales 2300, Australia.
authors.forename: Joerg
authors.initials: J
authors.lastname: Mattes
authors.affiliation: Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales 2300, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
authors.affiliation: 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.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Mackay
mesh_terms: D000085:Acetates / Q000378:metabolism* / Q000494:pharmacology; D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D004032:Diet; D004043:Dietary Fiber / Q000378:metabolism*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000187:drug effects; D005232:Fatty Acids, Volatile / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D051858:Forkhead Transcription Factors / Q000187:drug effects / Q000235:genetics; D000069196:Gastrointestinal Microbiome; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000187:drug effects / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D000085:Acetates; D004043:Dietary Fiber; D005232:Fatty Acids, Volatile; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012097:Repressor Proteins; C486545:Hdac9 protein, mouse; D006655:Histone Deacetylases