The respiratory tract microbiome and lung inflammation: a two-way street

Abstract

The lungs are not sterile or free from bacteria; rather, they harbor a distinct microbiome whose composition is driven by different ecological rules than for the gastrointestinal tract. During disease, there is often a shift in community composition towards Gammaproteobacteria, the bacterial class that contains many common lung-associated gram-negative "pathogens." Numerous byproducts of host inflammation are growth factors for these bacteria. The extracellular nutrient supply for bacteria in the lungs, which is severely limited during health, markedly increases due to the presence of mucus and vascular permeability. While Gammaproteobacteria benefit from airway inflammation, they also encode molecular components that promote inflammation, potentially creating a cyclical inflammatory mechanism. In contrast, Prevotella species that are routinely acquired via microaspiration from the oral cavity may participate in immunologic homeostasis of the airways.vAreas of future research include determining for specific lung diseases (1) whether an altered lung microbiome initiates disease pathogenesis, promotes chronic inflammation, or is merely a marker of injury and inflammation, (2) whether the lung microbiome can be manipulated therapeutically to change disease progression, (3) what molecules (metabolites) generated during an inflammatory response promote cross-kingdom signaling, and (4) how the lung "ecosystem" collapses during pneumonia, to be dominated by a single pathogen.

Figure 1

Comparison of the anatomy and bacterial microbiomes of the upper regions of the aerodigestive tract in humans. Bacterial composition is shown at the phylum-level. Gammaproteobacteria are a class in the Proteobacteria phylum. Arrows depict flow of air and microaerosols, with a greater contribution in most individuals during health coming from the oral cavity.

Figure 2

Model of the environmental, microbial, structural, and immunologic factors that control the composition of the lung microbiome during health and disease.