The Role of the Lung’s Microbiome in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease that commonly affects older adults and is associated with the histopathological and/or radiological patterns of usual interstitial pneumonia (UIP). Despite significant advances in our understanding of disease pathobiology and natural history, what causes IPF remains unknown. A potential role for infection in the disease’s pathogenesis and progression or as a trigger of acute exacerbation has long been postulated, but initial studies based on traditional culture methods have yielded inconsistent results. The recent application to IPF of culture-independent techniques for microbiological analysis has revealed previously unappreciated alterations of the lung microbiome, as well as an increased bacterial burden in the bronchoalveolar lavage (BAL) of IPF patients, although correlation does not necessarily entail causation. In addition, the lung microbiome remains only partially characterized and further research should investigate organisms other than bacteria and viruses, including fungi. The clarification of the role of the microbiome in the pathogenesis and progression of IPF may potentially allow its manipulation, providing an opportunity for targeted therapeutic intervention.

Early COVID-19 lockdown in Greece and idiopathic pulmonary fibrosis: a beneficial “impact” beyond any expectation

“…The development of an acute exacerbation (AE), histologically diffuse alveolar damage (DAD) upon UIP, represents the most devastating of its complications and leads to death the majority of patients admitted to intensive care unit (ICU) [2,3,4]. Viral infections in the setting of an altered host lung microbiome are likely important triggers of IPF-AE's and subsequent ARDS [4,5].…”

The Epithelial-Immune Crosstalk in Pulmonary Fibrosis

“…The advent of high throughput bacterial sequencing has allowed the identification of a diversified bacterial flora in healthy human lungs which showed modifications in chronic respiratory diseases ( 130 ). Current techniques are based on the sequencing of highly conserved genes, such as the 16S ribosomal RNA gene, to identify and quantify bacterial communities and cluster them into operational taxonomic units (OTU) ( 131 , 132 ). In the healthy lung, bacterial composition resembles the oropharyngeal flora and its structure is regulated through three mechanisms, namely the amount of bacterial immigration, the rate of elimination and the reproduction rate of local bacteria ( 133 ).…”

Lung inflammation in the pathogenesis of rheumatoid arthritis

“…There is also an emerging understanding of the microbiome in some lung diseases including emphysema, asthma, and IPF. [74][75][76] In particular, it is hypothesized that certain microbial factors may directly act at the lung epithelium driving local immune responses, 77 as well as that microbial interactions in the gut-lung axis may shape immunity that can lead to lung disease. 78 However, little is yet known about the microbiome and lung disease in RA, and this area needs exploration.…”

“…As to what environmental factors are critical to study going forward, there are established associations between factors such as tobacco smoke, occupational dust, and other inhaled factors with lung disease in RA. There is also an emerging understanding of the microbiome in some lung diseases including emphysema, asthma, and IPF . In particular, it is hypothesized that certain microbial factors may directly act at the lung epithelium driving local immune responses, as well as that microbial interactions in the gut‐lung axis may shape immunity that can lead to lung disease .…”