Therapeutic Targeting of the Respiratory Microbiome

The Respiratory Microbiome: An Important and Overlooked Source of Biological and Clinical Heterogeneity
Culture-independent microbiology has transformed our understanding of the respiratory microbiome in health and disease (1). Enabled by advances in next-generation sequencing and other technologies, we now appreciate the complexity of microbial communities within the respiratory tract, together with their metabolic, immunologic, and pathophysiologic consequences. Across the spectrum of acute and chronic respiratory disease, respiratory microbiota are detectable, viable, and variable across patients (2–5); correlated with disease status and severity (1); associated with airway and alveolar inflammation (5, 6); metabolically active and immunologically consequential (7, 8); predictive of clinical outcomes (9–11); influenced by environment and geography (6, 12); and causally involved in disease pathogenesis in animal models (11, 13).
Given these insights, we believe it is prudent to consider the respiratory microbiome as an unexploited, understudied therapeutic target: a biologically potent element of respiratory homeostasis, variable across patients, that may be more readily modifiable than other sources of patient heterogeneity, such as host genomes or comorbidities. In this Perspective, we delineate the anticipated opportunities and challenges related to clinically modulating the respiratory microbiome, which refers to the communities of microbes within the human respiratory tract and their associated ecological milieu. Our scope includes both acute and chronic respiratory diseases. For a broader discussion of the state of the field, including issues related to sampling, sequencing, analysis, and interpretation, we direct readers to recent reviews and monographs (1, 14–16).