Environmental exposures, the oral-lung axis and respiratory health: The airway microbiome goes on stage for the personalized management of human lung function.

The human respiratory system is constantly exposed to environmental stimuli, sometimes including toxicants, which can trigger dysregulated lung immune responses that lead to respiratory symptoms, impaired lung function and airway diseases. Evidence supports that the microbiome in the lungs has an indispensable role in respiratory health and disease, acting as a local gatekeeper that mediates the interaction between the environmental cues and respiratory health. Moreover, the microbiome in the lungs is intimately intertwined with the oral microbiome through the oral-lung axis. Here, we discuss the intricate three-way relationship between (i) cigarette smoking, which has strong effects on the microbial community structure of the lung; (ii) microbiome dysbiosis and disease in the oral cavity; and (iii) microbiome dysbiosis in the lung and its causal role in patients suffering chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. We highlight exciting outcomes arising from recently established interactions in the airway between environmental exposures, microbiome, metabolites-functional attributes and the host, as well as how these associations have the potential to predict the respiratory health status of the host through an airway microbiome health index. For completion, we argue that incorporating (synthetic) microbial community ecology in our contemporary understanding of lung disease presents challenges and also rises novel opportunities to exploit the oral-lung axis and its microbiome towards innovative airway disease diagnostics, prognostics, patient stratification and microbiota-targeted clinical interventions in the context of current therapies.