Abstract
Idiopathic pulmonary fibrosis (IPF) is an incurable disease with poor prognosis and unknown etiology. The poor clinical outcome is associated with enhanced microbial burden in bronchoalveolar lavage fluid from IPF patients. However, whether microbes from the respiratory tract fluid cause the disease remains uncertain. Tissue-associated microbes can influence host physiology in health and disease development. The aim of this study was to evaluate the existence of microbes in lung fibrotic tissues. We evaluated the microbial community in lung tissues from IPF and from human transforming growth factor-β1 (TGF-β1) transgenic mice with lung fibrosis by oligotyping. We also evaluated the microbial population in non-tumor-bearing tissues from surgical specimens of lung cancer patients. The phyla Firmicutes and the genus Clostridium tended to be predominant in the lung tissue from IPF and lung cancer patients. Oligotyping analysis revealed a predominance of bacteria belonging to the genera Halomonas, Shewanella, Christensenella, and Clostridium in lung tissue from IPF and lung cancer. Evaluation of the microbial community in the lung tissue from mice revealed abundance of Proteobacteria in both wild-type (WT) littermates and transgenic mice. However, the genus Halomonas tended to be more abundant in TGF-β1 transgenic mice compared to WT mice. In conclusion, this study describes tissue-associated microbes in lung fibrotic tissues from IPF patients and from aging TGF-β1 transgenic mice.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with a median survival of only 2–4 years following diagnosis, and it is considered to be more lethal than many types of cancer (King et al, 2011)
Luminal (BALF) and Saliva Samples Analysis of bacterial communities by 16S rRNA gene amplicon sequencing revealed a trend toward enhanced proportion of Proteobacteria in saliva and bronchoalveolar lavage fluid (BALF) of IPF patients compared to healthy subjects (Figure 1A and Supplementary Tables 3, 4)
Subsequent evaluation at the genus level showed that Halomonadaceae and Shewanellaceae, both members of the Proteobacteria, tended to be more dominant in saliva and BALF from IPF patients compared to healthy subjects
Summary
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with a median survival of only 2–4 years following diagnosis, and it is considered to be more lethal than many types of cancer (King et al, 2011). Recent studies suggest that imbalance of the lung microbial community or dysbiosis may play a role in the process of chronic injury and activation of lung epithelial cells in IPF (Molyneaux and Maher, 2013; Hewitt and Molyneaux, 2017). The association of the lung microbiota with acute exacerbation, clinical progression of the disease, risk of death, decline in pulmonary function, persistent elevation of the host immune response and with the progression-free survival, and fibroblast responsiveness provides strong evidence on the clinical and pathogenic relevance of the lung microbiota in IPF (Molyneaux et al, 2014; Huang et al, 2017; Wang et al, 2017). Whether the lung microbial population is the cause or consequence of IPF remains unknown
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