Insights into respiratory microbiome composition and systemic inflammatory biomarkers of bronchiectasis patients.

Abstract

The human microbiomes, including the ones present in the respiratory tract, are described and characterized in an increasing number of studies. However, the composition and the impact of the healthy and/or impaired microbiome on pulmonary health and its interaction with the host tissues remain enigmatic. In chronic airway diseases, bronchiectasis stands out as a progressive condition characterized by microbial colonization and infection. In this study, we aimed to investigate the microbiome of the lower airways and lungs of bronchiectasis patients together with their serum cytokine and chemokine content, and gain novel insights into the pathogenesis of bronchiectasis. The microbiome of 47 patients was analyzed by sequencing of full-length 16S rRNA gene using amplicon sequencing Oxford Nanopore technologies. Their serum inflammatory mediators content was quantified in parallel. Several divergently composed microbiome groups were identified and characterized, the majority of patients displayed one dominant bacterial species, whereas others had a more diverse microbiome. The analysis of systemic immune biomarkers revealed two distinct inflammatory response groups, i.e., low and high response groups, each associated with a specific array of clinical symptoms, microbial composition, and diversity. Moreover, we have identified some microbiome compositions associated with high inflammatory response, i.e., high levels of pro- and anti-inflammatory cytokines, whereas other microbiomes were in correlation with low inflammatory responses. Although bronchiectasis pathogenetic mechanisms remain to be elucidated, it is clear that addressing microbiome composition in the airways is a valuable resource not only for diagnosis but also for personalized disease management.

Importance: The population of microorganisms on/in the human body resides in distinct local microbiomes, including the respiratory microbiome. It remains unclear what defines a healthy and a diseased respiratory microbiome. We investigated the respiratory microbiome in chronic pulmonary infectious disease, i.e., bronchiectasis, and researched correlations between microbiome composition, systemic inflammatory biomarkers, and disease characteristics. The bronchoalveolar microbiome of 47 patients was sequenced, and their serum inflammatory mediators were quantified. The microbiomes were grouped based on their content and diversity. In addition, patients were also grouped into low- and high-response groups according to their inflammatory biomarkers' levels. Certain microbiome compositions, mainly single-species dominated, were associated with high levels of inflammatory cytokines, whereas others correlated with low inflammatory response and remained diverse. We conclude that respiratory microbiome composition is a valuable resource for the diagnostics and personalized management of bronchiectasis, which may include preserving microbiome diversity and introducing possible probiotics.