The lung microbiome in interstitial lung disease

Abstract

Interstitial lung disease (ILD) is a heterogeneous chronic form of lung disease. The pathogenesis of ILD is poorly understood and a common form of ILD, idiopathic pulmonary fibrosis (IPF) is associated with poor prognosis. There is evidence for substantial dysregulated immune responses in ILD. The microbiome is a key regulator of the immune response, and the lung microbiome correlates with alveolar immunity and clinical outcomes in ILD. Most observational lung microbiome studies have been conducted in patients with IPF. A consistent observation in these studies is that the bacterial burden of the lung is elevated in patients with IPF and predicts mortality. However, our understanding of the mechanism is incomplete and our understanding of the role of the lung microbiome in other forms of ILD is limited. The microbiomes of the oropharynx and gut may have implications for the lung microbiome and pulmonary immunity in ILD but require substantial further research. Here, we discuss the studies supporting a role for the lung microbiome in the pathogenesis of IPF, and briefly describe the putative role of the oral-lung axis and the gut-lung axis in ILD.

FIGURE 1

The lung microbiome in interstitial lung disease and the gut– and oral–lung axis. a) The oral–lung axis describes the immigration of oral microbiota to the lung across the respiratory tract by microaspiration. b) The gut–lung axis describes the potential impact of gut microbiota and its products on lung immunity and disease, including modification of regulatory T cells and innate lymphoid cells, the effect of circulating gut microbiota short-chain fatty acids and microbial ligands on bone marrow granulopoiesis, and the translocation of bacteria to the lung in addition to other mechanisms. c) The lung microbiome in idiopathic pulmonary fibrosis is characterised by an increased bacterial burden compared to healthy volunteers. Putative mechanisms associated with lung fibrosis include the production of bacteria-derived toxins such as pneumolysin (Streptococcus pneumonia) [32] and corisin (Staphylococcus genus) [33] and interactions between lung microbiota and interleukin (IL)-17 production by macrophages [22].