Lung microbiome and host immune tone in subjects with idiopathic pulmonary fibrosis treated with inhaled interferon-γ

Therapies targeting inflammation reveal inconsistent results in idiopathic pulmonary fibrosis(IPF). Aerosolised interferon (IFN)-γ has been proposed as a novel therapy. Changes in the host airway microbiomeare associated with the inflammatory milieu and may be associated with disease progression. Here, we evaluate whether treatment with aerosolised IFN-γ in IPF impacts either the lower airway microbiomeor the host immune phenotype. Patients with IPF who enrolled in an aerosolised IFN-γ trial underwent bronchoscopy at baseline and after 6 months. 16S rRNA sequencing of bronchoalveolar lavage fluid (BALF) was used to evaluate the lung microbiome. Biomarkers were measured by Luminex assay in plasma, BALF and BAL cell supernatant. The compPLS framework was used to evaluate associations between taxa and biomarkers. IFN-γ treatment did not change α or β diversity of the lung microbiomeand few taxonomic changes occurred. While none of the biomarkers changed in plasma, there was an increase in IFN-γ and a decrease in Fit-3 ligand, IFN-α2 and interleukin-5in BAL cell supernatant, and a decrease in tumour necrosis factor-β in BALF. Multiple correlationsbetween microbial taxa common to the oral mucosaand host inflammatory biomarkers were found. These data suggest that the lung microbiomeis independently associated with the host immune tone and may have a potential mechanistic role in IPF.