Community ecology: The framework for next steps in microbiome research in chronic airway disease

The next frontier in respiratory microbiome research is to elucidate functional interactions between microbes and their host, and to understand how this partnership evolves across respiratory health, early disease and progression. To fully appreciate how this dynamic partnership is tuned and perturbed, the lens of community ecology serves as a useful framework (figure 1). Building on recent advances in defining respiratory microbiota composition, the field is poised for significant expansion as emerging tools enable functional insights that are directly translatable to clinical contexts. These contexts include application to disease endophenotyping and potential prediction of treatment outcomes. While compositional surveys remain necessary, the field must increasingly connect community shifts to functional outputs through metagenomics, meta-transcriptomics, metabolomics, single-cell and spatial approaches, and advanced model systems. Challenges with applying certain techniques to airway specimens are acknowledged, particularly if studying healthy persons, those with earlier stage disease, or longitudinally. Complementarily, new experimental models and platforms that better approximate airway physiology and microanatomy can promote enhanced understanding of microbe-host interactions, including polymicrobial interactions in the airway. Anticipated advances in understanding how the airway microbiome supports respiratory health, and possibly attenuation of disease risk or progression, will pave the way for more targeted strategies to intervene on the burden of chronic airway diseases.