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

By A. Thorburn, Craig I. McKenzie, S. Shen, D. Stanley, L. Macia, L. Mason, Laura K. Roberts, Connie H. Y. Wong, Raymond Shim, R. Robert and 12 more. Nature Communications, 2015

811 citations recorded by the source corpus.

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. Growing evidence suggests that environmental rather than genetic factors are major contributors to asthma development. Here the authors show that high intake of dietary fibre by pregnant mice increases resistance of their progeny to the development of allergic airways disease.

Subfields: Immunology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/0facd089685b5f52ef0c2c192b3895a582834ca5

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Citations in the corpus

From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. (2016, positive): “A high-fiber diet (producing high amounts of acetate) suppresses allergic airway disease by enhancing regulatory T cells (Treg) through HDAC9 inhibition (Thorburn et al., 2015).”
Short chain fatty acids and its producing organisms: An overlooked therapy for IBD? (2021, background): “For example, although acetate did not show a direct inhibition of the HDAC mechanism [56], administration of acetate was shown to have protective effects, mediated by HDAC inhibition [55].”
Metabolomics for Investigating Physiological and Pathophysiological Processes. (2019, methodology): “In a more recent study using the same HDM asthma mouse model, maternal intake of acetate was shown to reduce allergic airways disease in offspring (462).”