Extracellular iron and the lung microbiome in smoking and COPD

Most microorganisms that make up the lung microbiome use several iron acquisition strategies for survival. Iron levels and iron-associated proteins are higher in the bronchoalveolar lavage fluid (BALF) of smokers with and smokers without COPD associating with disease severity. In this study we assessed whether or not smokers with and smokers without COPD who have increased airway iron display a specifically altered airway microbiome.

16S ribosomal RNA gene sequencing of BALF from individuals (n=181) enrolled in the bronchoscopy substudy of the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) was paired with measured levels of BALF iron, the iron storage protein ferritin (ex-ferritin) and the host-iron siderophore lipocalin-2 (LCN-2) in matched participants.

Overall, iron, ex-ferritin and LCN-2 levels were not associated with ecological diversity metrics in the BALF of participants enrolled in this cohort. However, in a differential analysis, specific taxa were found to be enriched in never-smokers with low BALF ex-ferritin levels and also in smokers with high BALF iron levels. Of participants with COPD, an unclassified taxon, Bacteroidetes-OTU0063, was enriched in those with a high BALF iron level and those with a low BALF LCN-2 level. Furthermore, COPD participants with a high number of historical exacerbations and a high BALF LCN-2 level showed enrichment for Streptococcus and Leptotrichia. Leptotrichia was also enriched in participants with COPD and a high number of historical exacerbations with elevated BALF iron and BALF ex-ferritin levels. In addition, symptomatic individuals with COPD who had a high BALF ex-ferritin level had enrichment with Moraxella.

The above data suggest that abundance of iron and iron-binding proteins may be linked to the presence of both oral commensals and potentially pathogenic microorganisms in the lower airways of individuals with COPD.