Corticosteroids treatment alters lung and gut microbiome communities that correlates to increased pathologic immune responses

Abstract

Abstract Inhaled corticosteroid (ICS) are recommended as first-line controller medications for persistent asthma. Microbial interaction among the gut-lung axis has been suggested. The impact of this crosstalk can modify homeostasis and disease development by altering the host’s immune responses and metabolic status. In this work, we investigated the effect of ICS on microbiome during chronic allergic pulmonary disease. Here we demonstrated that the alternations of lung and gut microbiome can be linked to higher immunological response in mice treated with ICS with Respiratory syncytial virus (RSV) infection. We observed that ICS use during chronic allergy protected the mice, as expected, from lung inflammation and mucus deposition. However, the lung and gut microbiome also presented significant alterations in both naïve mice treated with ICS alone or in ICS asthmatic mice. Microbiome analysis revealed that the principal component analysis of lung and cecum samples in the ICS groups are significantly different from other groups suggesting that ICS impacts the lung and gut microbiome directly with specific organisms altered. When we RSV infected naïve mice treated with ICS, compared to naïve without ICS we observed significant worse pathologic responses. qPCR analysis of Th2-cytokines and of mucus gene showed significantly higher expression in naïve mice treated with ICS than control treated RSV infected mice. Altogether, alternations of lung and gut microbiome can be associated with treatment with ICS with higher immunological response in naïve mice with ICS after RSV infection. Our future studies will focus on how the changed microbiome modifies the subsequent immune responses by focusing on local lung and systemic metabolite changes.