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Deciphering the Lung Microbiome: Implications for Lung Health and Disease

The human microbiome, composed of the aggregate of the microorganisms and their composite genetic material that exists within and upon the human body, is a rich operational ecosystem that greatly contributes to physiologic homeostasis and critical functioning. Individual differences in the microbiota are believed to contribute to the variability of disease incidence and expression and, ultimately, may present an opportunity for therapeutic manipulation and targeted precision medicine. Our advancing understanding of the microbiome, predicated upon the development and availability of rapid-sequence culture-independent molecular techniques to assess for microorganisms and genetic signatures, has refuted the long-standing belief that the lung is sterile. These culture-independent techniques based on molecular analysis including 16S rRNA and whole gene sequencing have identified a robust environment of microorganisms not previously easily recognized using traditional culture-based methodology. Relative to our understanding of the gut and skin microbiome, characterization of the lung microbiome is lagging due to difficulties in characterization and delayed recognition of its richness. However, progressively expanding investigations coupled with greater availability of microbiome analysis are broadening our understanding of the healthy lung microbiome [1] and aberrations in disease states. Characterizing the lung microbiome has unique inherent challenges primarily due to (1) less abundant volume than skin or gut microbiome, (2) variation by regional geography within the lung, and (3) the potential for specimen contamination by the oral and nasal cavity microbiome. The biomass of the lung microbiota is of markedly lower magnitude than other human microbiota. Unlike the GI tract, which is of uniform temperature and through which movement is unidirectional, there is a dramatic temperature gradient between the larynx and distal alveolus and the movement of air and microorganisms is bidirectional in the lung. Furthermore, the lipidrich surfactant covering the bulk of the area of the respiratory tree exerts a biostatic effect [2]. Collectively, these factors are believed to suppress microbial growth. Variation in microbiome has been demonstrated by comparative analysis of sampling in diverse anatomic locations in the lung within in an individual with advanced lung disease [3] although the regional variation in pulmonary microbiota in healthy subjects appears much less robust [4]. This regional variation obfuscates investigations and comparative studies in diseased lungs. Furthermore, insertion of a bronchoscope via a nasal or oral route allows for contamination of specimens collected from the lower airway with the oral or nasal microbiome. Our understanding of the role of the pulmonary microbiome in disease is nascent but rapidly advancing. An analysis of the microbiome of patients with asthma obtained via a protected specimen brush demonstrated notable difference as compared with normal controls [5].