Respiratory microbiome dysbiosis and temporal dynamics in individuals with asthma.

Abstract Microbiome dysbiosis across the respiratory tract has been implicated in the development and exacerbations of asthma. Little is known regarding the short-term temporal variability of the respiratory microbiome in health and asthma. In this study, we evaluate six scenarios of dysbiosis by investigating the inter- and intra-individual variability of the nasopharyngeal microbiome, measured with metagenomic sequencing. We characterized 239 microbiome samples from thirteen healthy individuals and from seventeen patients with well-controlled mild to moderate persistent asthma collected during a one-month period in which patients experienced no asthma exacerbations or infections. We controlled for sex, age (range 5 to 38 years), population (Greece and Poland), and microbiome type, for multiple levels of species incidence (expanded to core). Microbiomes collected from the same individual at different time points were more similar than those collected from the same group (health or asthma), but some individuals’ microbiomes were more variable than others. Microbiomes drawn from asthma patients were less likely to resemble each other than the microbiomes of healthy individuals, suggesting increased inter-sample variability and susceptibility to stochastic changes in asthma. In addition, the microbiomes of asthma patients became increasingly dissimilar over time, suggesting increased intra-individual temporal dynamics. Finally, microbiomes of individuals with asthma were more diverse than those of healthy individuals, while species diversity was negatively associated with temporal change in both the asthma and health groups. We propose that the increased diversity, inter-sample variability and intra-individual temporal dynamics during stable disease state(s) are intrinsic properties of the microbial system in asthma and characterise dysbiosis. Our work has significant implications for the relevance of the respiratory microbiome in asthma.