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 alters the microbiome in conjunction with immune responses presents striking data. The overall findings identify that although 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-17 expression. Analysis of the lung and gut microbiome suggested that there are differences in RSV exacerbation that are further altered by fluticasone (FLUT) treatment. Using metagenomic inference software, PICRUSt2, we were able to predict that the metabolite profile produced by the changed gut microbiome was significantly different with multiple metabolic pathways and associated with specific treatments with or without FLUT. Importantly, measuring plasma metabolites in an unbiased manner, our data indicate that there are significant changes associated with chronic allergen exposure, RSV exacerbation, and FLUT treatment that are reflective of responses to the disease and treatment. In addition, the changes in metabolites appeared to 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 lung FLUT before RSV infection. The naïve animals treated with FLUT before RSV infection demonstrated enhanced disease that corresponded to an altered microbiome and the related PICRUSt2 metagenomic inference analysis. Altogether, these findings set the foundation for identifying important correlations of severe viral exacerbated allergic disease with microbiome changes and the relationship of host metabolome with a potential for early life pulmonary steroid influence on subsequent viral-induced disease.NEW & NOTEWORTHY These studies outline a novel finding that airway treatment with fluticasone, a commonly used inhaled steroid, has significant effects on not only the local lung environment but also on the mucosal microbiome, which may have significant disease implications. The findings further provide data to support that pulmonary viral exacerbations of asthma with or without steroid treatment alter the lung and gut microbiome, which have an impact on the circulating metabolome that likely alters the trajectory of disease progression.