The emerging role of the lung microbiome and its importance in non-small cell lung cancer diagnosis and treatment

Over the last 10 years, with the development of culture-free bacterial identification techniques, understanding of how the microbiome influences diseases has increased exponentially and has highlighted potential opportunities for its use as a diagnostic biomarker and interventional target in many diseases including malignancy. Initial research focused on the faecal microbiome since it contains the densest bacterial populations and many other mucosal sites, such as the lungs, were until recently thought to be sterile. However, in recent years, it has become clear that the lower airways are home to a dynamic bacterial population sustained by the migration and elimination of microbes from the gastrointestinal and upper airway tracts. As in the gut, the lung microbiome plays an important role in regulating mucosal immunity and maintaining the balance between immune tolerance and inflammation. Studies to date have all shown that the lung microbiome undergoes significant changes in the setting of pulmonary disease. In lung cancer, animal models and small patient cohort studies have suggested that microbiome dysbiosis may not only impact tumour progression and response to therapy, particularly immunotherapy, but also plays a key role in cancer pathogenesis by influencing early carcinogenic pathways. These early results have led to concerted efforts to identify microbiome signatures that represent diagnostic biomarkers of early-stage disease and to consider modulation of the lung microbiome as a potential therapeutic strategy. Lung microbiome research is in its infancy and studies to date have been small, single centre with significant methodological variation. Large, multicentre longitudinal studies are needed to establish the clinical potential of this exciting field.