The Lung Microbiome, Immunity, and the Pathogenesis of Chronic Lung Disease

Abstract

The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared with the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration, and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen, and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships.

Figure 1. Proposed regulation of disease exacerbation by the gut-lung axis

During normal homeostasis, the lung microbiome is primarily characterized by low biomass, but prominent diversity in microbial species. In contrast, the healthy gut microbiome is characterized by high diversity and high biomass. In homeostasis, the gut microbiome helps shape development of lymphoid architecture and appropriate immune responsiveness. Loss of gut diversity (e.g. as a result of viral infection or antibiotic use) may cause dysregulation of IL-17 or bacterial killing mechanisms systemically; potentially leading to impaired alveolar macrophage function and the overgrowth of selective organisms with pathogenic potential that may result in disease exacerbation. Alternatively, some forms of chronic lung disease exacerbations may be due to translocation and/or expansion of bacterial contents from the gut. Direct insults to the lung (e.g. viral infection or aspiration) may exacerbate disease in part via their effects on the lung or gut microbiota. Alterations in systemic cytokines (e.g. Th2 or Th17 induction) may promote pathologic fibrotic remodeling as well.