Whole genome sequencing of the pulmonary microbiome in interstitial lung disease subtypes

Interstitial lung diseases (ILDs) represent a heterogeneous group of lung disorders, some of which remain unclassifiable. The pulmonary microbiome may contribute to ILD pathogenesis, yet research is limited. Whole genome sequencing (WGS) offers enhanced microbial characterization. Here we evaluate the dysbiosis index (DI) as a potential biomarker to refine the classification of unclassifiable ILD.

Protected bronchoalveolar lavage (PBAL) samples were collected from the right middle lobe of 12 IPF patients, 34 sarcoidosis patients, 11 unclassifiable ILD patients and 100 healthy controls. WGS was performed with the Illumina NovaSeq platform. Operational Taxonomic Units (OTU) were identified with GAIA 2.0 software, and statistical analyses were performed in R. The DI was calculated based on differential abundant species.

Alpha diversity was significantly higher in IPF and sarcoidosis patients compared to healthy controls. Beta diversity analysis revealed distinct microbial composition in IPF, sarcoidosis and unclassifiable ILD groups relative to controls. Differential abundance analysis identified several taxa with significant variation across groups. Notably, the dysbiosis index demonstrated high sensitivity and specificity in distinguishing IPF and sarcoidosis from healthy controls and provided further insight into the microbial characterization of unclassifiable ILD.

The pulmonary microbiome in unclassifiable ILD patients differed from healthy controls, and the dysbiosis index may provide exploratory insights for future ILD characterization.