From the nose to the lungs: the intricate journey of airborne pathogens amid commensal bacteria

The recent COVID-19 pandemic has dramatically brought the pitfalls of airborne pathogens to the attention of the scientific community. Not only viruses but also bacteria and fungi may exploit air transmission to colonize and infect potential hosts and be the cause of significant morbidity and mortality in susceptible populations. The efforts to decipher the mechanisms of path-ogenicity of airborne microbes have brought to light the delicate equilibrium that governs the homeostasis of mucosal mem-branes. The microorganisms already thriving in the permissive environment of the respiratory tract represent a critical component of this equilibrium and a potent barrier to infection by means of direct competition with airborne pathogens or indirectly via modulation of the immune response. Moving down the respiratory tract, physicochemical and biological con-straints promote site-specific expansion of microbes that engage in cross talk with the local immune system to maintain home-ostasis and promote protection. In this review, we critically assess the site-specific microbial communities that an airborne pathogen encounters in its hypothetical travel along the respiratory tract and discuss the changes in the composition and function of the microbiome in airborne diseases by taking fungal and SARS-CoV-2 infections as examples. Finally, we discuss how technological and bioinformatics advancements may turn microbiome analysis into a valuable tool in the hands of clini-cians to predict the risk of disease onset, the clinical course, and the response to treatment of individual patients in the direc-tion of personalized medicine implementation.