S18 Streptococcus is enriched in the gut microbiome in idiopathic pulmonary fibrosis and associated with worse survival

Introduction
Idiopathic pulmonary fibrosis (IPF) is a progressive and incurable lung disease with a median survival of less than four years. Disturbance of the lung microbiome has been identified as a potential risk factor for the development and progression of IPF, and may play a mechanistic role in fibrogenesis. Despite growing evidence that changes to the gut microbiome can contribute to the pathogenesis of respiratory conditions, its role in IPF is poorly understood. We therefore aimed to investigate the associations between the gut microbiome and disease behaviour in IPF.

Methods
Incident cases of IPF and healthy controls were recruited prospectively. OMNIgene GUT sample collection kits were sent to participants, returned by post, and frozen prior to processing. 16S rRNA gene sequencing of the v4 hypervariable region was performed on DNA extracted from stool samples. Following comparisons with healthy controls, the inferred functional potential of the IPF microbiota and associations with progression-free survival were explored.

Results
Stool samples were collected from 184 patients with IPF and 146 healthy controls. The IPF cohort was predominantly male (86.8%) with a median age of 75.1 years. The majority were either current or former smokers (74.2%). Lung function was impaired, with a mean forced vital capacity (FVC) of 78.2% predicted (±SD 14.3), and a diffusing capacity of the lung for carbon monoxide (DLCO) of 49.4% predicted (±SD 13.5). The gut microbiome in IPF was significantly different to that of healthy controls, driven by the enrichment of Streptococcus. Age and reflux treatment also influenced microbial composition, with therapy for reflux driving changes in both health and disease. In patients with IPF, a higher abundance of Streptococcus was associated with significantly worse progression-free survival. Inferred functional analysis showed a higher abundance of microbial pathways involved in host invasion and infection in IPF, including endocytosis, bacterial invasion of epithelial cells, and Staphylococcus aureus infection.

Conclusions
There are significant alterations in the gut microbiome in patients with IPF, driven by an increased abundance of Streptococcus. These changes may contribute to pathogenesis and disease progression.