AUTHOR=Yoon Hee-Young , Moon Su-Jin , Song Jin Woo 

TITLE=Lung Tissue Microbiome Is Associated With Clinical Outcomes of Idiopathic Pulmonary Fibrosis

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.744523

DOI=10.3389/fmed.2021.744523

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Several studies using bronchoalveolar lavage fluid (BALF) reported that lung microbial communities were associated with the development and clinical outcome of idiopathic pulmonary fibrosis (IPF). However, the microbial communities in IPF lung tissues are not well known. This study is aimed to investigate bacterial microbial communities in lung tissues and determine their impact on the clinical outcomes of patients with IPF.</p><p><bold>Methods:</bold> Genomic DNA extracted from lung tissues of patients with IPF (<italic>n</italic> = 20; 10 non-survivors) and age- and sex-matched controls (<italic>n</italic> = 20) was amplified using fusion primers targeting the V3 and V4 regions of the 16S RNA genes with indexing barcodes.</p><p><bold>Results:</bold> Mean age of IPF subjects was 63.3 yr, and 65% were male. Alpha diversity indices did not significantly differ between IPF patients and controls, or between IPF non-survivors and survivors. The relative abundance of <italic>Lactobacillus, Paracoccus</italic>, and <italic>Akkermansia</italic> was increased, whereas that of <italic>Caulobacter, Azonexus</italic>, and <italic>Undibacterium</italic> decreased in patients with IPF compared with that in the controls. A decreased relative abundance of <italic>Pelomonas</italic> (odds ratio [OR], 0.352, <italic>p</italic> = 0.027) and <italic>Azonexus</italic> (OR, 0.013, <italic>p</italic> = 0.046) was associated with a diagnosis of IPF in the multivariable logistic analysis adjusted by age and gender. Multivariable Cox analysis adjusted for age and forced vital capacity (FVC) revealed that higher relative abundance of <italic>Streptococcus</italic> (hazard ratio [HR], 1.993, <italic>p</italic> = 0.044), <italic>Sphingomonas</italic> (HR, 57.590, <italic>p</italic> = 0.024), and <italic>Clostridium</italic> (HR, 37.189, <italic>p</italic> = 0.038) was independently associated with IPF mortality. The relative abundance of <italic>Curvibacter</italic> (<italic>r</italic> = 0.590) and <italic>Thioprofundum</italic> (<italic>r</italic> = 0.373) was correlated positively, whereas that of <italic>Anoxybacillus</italic> (<italic>r</italic> = −0.509) and <italic>Enterococcus</italic> (<italic>r</italic> = −0.593) was correlated inversely with FVC. In addition, the relative abundance of the <italic>Aquabacterium</italic> (<italic>r</italic> = 0.616) and <italic>Peptoniphilus</italic> (<italic>r</italic> = 0.606) genera was positively correlated, whereas that of the <italic>Fusobacterium</italic> (<italic>r</italic> = −0.464) and <italic>Phycicoccus</italic> (<italic>r</italic> = −0.495) genera was inversely correlated with distance during the 6-min walking test.</p><p><bold>Conclusions:</bold> The composition of the microbiome in lung tissues differed between patients with IPF and controls and was associated with the diagnosis, mortality, and disease severity of IPF.</p>