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

TLDR

Asthma is common in Western societies, with environmental factors and gut microbiota increasingly recognized as key contributors. The study investigates whether maternal intake of dietary fibre or acetate can prevent allergic airway disease in offspring. Pregnant mice were fed high‑fibre or acetate diets, and the resulting gut microbiota changes and epigenetic modifications were examined in adult offspring and fetal lungs. Maternal high‑fibre/acetate feeding increased acetate production, enhanced T‑reg numbers and Foxp3 acetylation via HDAC9 inhibition, suppressed asthma‑linked genes in fetal lungs, and conferred resistance to allergic airway disease in adult progeny, suggesting a preventive strategy.

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. 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.