Microbiome modifications by steroids during viral exacerbation of asthma and in healthy mice.

Abstract

In the present studies the assessment of how viral exacerbation of asthmatic responses with and without pulmonary steroid treatment altered the microbiome in conjunction with immune responses presents striking data. The overall findings identify that while steroid treatment of allergic animals diminished the severity of the respiratory syncytial virus (RSV)-induced exacerbation of airway function and mucus hypersecretion, there were local increases in IL-17A expression. Analysis of lung and gut microbiome suggested that there are differences in the RSV exacerbation that are further altered by fluticasone (FLUT) treatment. Using metagenomic inference software, PICRUSt2, we were able to predict that the metabolite profile that the changed gut microbiome produced was significantly different with multiple metabolic pathways and associated with specific treatments with or without FLUT. Importantly, measuring plasma metabolites, our data indicate that there are significant changes associated with chronic allergen exposure, RSV exacerbation, and with FLUT treatment. The changes to the metabolites have contributions from both host and microbial pathways. To understand if airway steroids on their own altered lung and gut microbiome along with host responses to RSV infection, naïve animals were treated with FLUT prior to RSV infection. The naïve animals with FLUT prior to RSV infection demonstrated enhanced disease corresponding to altered microbiome and the PICRUSt2 metagenomic inference analysis. Altogether, these findings set the foundation for identifying important correlations of severe viral exacerbated allergic disease with microbiome changes a potential for early life pulmonary steroid influence on subsequent viral induced disease.