The lung microbiome: progress and promise

Abstract

The healthy lung was long thought of as sterile, but recent advances using molecular sequencing approaches have detected bacteria at low levels. Healthy lung bacteria largely reflect communities present in the upper respiratory tract that enter the lung via microaspiration, which is balanced by mechanical and immune clearance and likely involves limited local replication. The nature and dynamics of the lung microbiome, therefore, differ from those of ecological niches with robust self-sustaining microbial communities. Aberrant populations (dysbiosis) have been demonstrated in many pulmonary diseases not traditionally considered microbial in origin, and potential pathways of microbe-host crosstalk are emerging. The question now is whether and how dysbiotic microbiota contribute to initiation or perpetuation of injury. The fungal microbiome and virome are less well studied. This Review highlights features of the lung microbiome, unique considerations in studying it, examples of dysbiosis in selected disease, emerging concepts in lung microbiome-host interactions, and critical areas for investigation.

Figure 1. Ecological dynamics of the lung microbiome.

The lung microbiome is determined by the balance between immigration from the URT and elimination via immune and mechanical processes. In healthy lungs, local microbial replication in the airways and lung parenchyma is limited. In lung disease, structural disturbances and alterations to the local environment favor microbial growth, which predominantly determines lung microbial composition.

Figure 2. Nature and potential impact of the lung microbiome in health and disease.

In healthy lungs, the bacterial communities (colored shapes) have low biomass and are largely derived passively from the URT. Low-biomass communities associate with a balanced immune tone that promotes mucosal regulatory T cells (Tregs) and Th17 readiness. Tregs and Th17 cells may promote a basal-level immune tone that is necessary for clearance of encountered pathogens without pathological inflammatory responses. In disease, a dysbiotic microbiota may activate innate and adaptive immune responses that promote immunopathology. This inflammatory state can lead to epithelial fibroproliferation, promotion of immune cell immigration to the lung in response to cytokine and chemokine elaboration, and heightened Th2 immune tone, among other potential pathological mechanisms. Mediators include microbial metabolites such as short-chain fatty acids (SCFAs), as well as pattern recognition receptor (PRR) ligands by which even nonviable bacteria may trigger responses. The virome and mycobiome in health and lung disease remain understudied.