Live bacteria in gut microbiome dictate asthma onset triggered by environmental particles via modulation of DNA methylation in dendritic cells.

Abstract

Despite broad knowledge of the pathogenesis, our understanding of the origin of allergy and asthma remains poor, preventing etiotropic treatments. The gut microbiome is seen to be altered in asthmatics; however, proof of causality of the microbiome alterations is lacking. We report on gut microbiome transplantation (GMT) from mice predisposed to asthma by maternal exposure to pro-allergy environmental particles into naive recipients. This GMT confers asthma predisposition, and the effect is abrogated by gamma sterilization of the transplant material or by co-administration of antibacterials, indicating that viable bacteria are mediating the effect. Metagenomics identifies key changes in the "pro-asthma" microbiome, and metabolomics links the identified species to altered production of butyrate known to act on immune cells and epigenetic mechanisms. We further show that transplant recipients develop DNA methylation alterations in dendritic cells. Finally, dendritic cells with an altered methylome present allergen to T cells, and this effect is abrogated by an epigenetically acting drug in vitro.