Uncovering the hidden villain within the human respiratory microbiome

Respiratory tract infection increases the risk of secondary bacterial infection and causes mortality. Despite advances in the field of targeted molecular diagnostics, there are still failed attempts in identifying a valid causative etiological agent in a large proportion of respiratory tract infections. To date, a comprehensive list of human respiratory infection-associated eukaryotic viruses has been identified. However, there has been little progress towards the characterisation of the viruses that infect bacteria (phages), which are capable of mediating the transfer of virulence genes into non-pathogenic bacterial species to cause respiratory tract infections. With the advent of next-generation-sequencing, the application of an unbiased comparative metagenomic survey on the viral communities within the human respiratory tract may reveal to us how the phage virome changes between healthy individuals and respiratory tract infection patients. With this useful information, it will be feasible to develop an alternative phage-based diagnostic panel for respiratory tract infections. The review herein presents the current status of human airway microbiome research and highlights potential gaps which can be translated into research possibilities for future work on respiratory tract infection diagnosis.