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.


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*


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