LUMI study represents a focused effort to investigate the lung parenchymal microbiota and its potential role in PAH pathophysiology.

The bronchial airways are known to harbor a metabolically active microbiota essential for respiratory health, but the human lung parenchyma has long been considered nearly sterile due to its inaccessibility and extremely low microbial biomass. A comprehensive and rigorous protocol was developed to investigate the pulmonary microbiome in lung tissue, focusing on improved bacterial DNA extraction, removal of human DNA, and the inclusion of multiple negative controls to detect any contamination. This approach was applied to lung biopsies from 45 patients with pulmonary arterial hypertension (PAH) and 14 controls, using both 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing. With strict controls in place, no consistent core microbiota was detected in lung tissue from uninfected patients. After extensive decontamination, most initially detected bacterial taxa were eliminated as likely contaminants or sequencing artifacts. Only a small set of genera were identified by both 16S and shotgun methods, all of which are common skin commensals, suggesting they were introduced via the biopsy procedure. In conclusion, we found no evidence of a resident bacterial community in the lung parenchyma of PAH patients or controls without infection. Our findings indicate that lung tissue may lack a true microbiota, highlighting the importance of stringent protocols to discern true signals from contamination in low-biomass microbiome studies.