CURE will go beyond the state of the art by using the deep analytical power of metagenomics to 1) fully reconstruct for the first time the complete microbiome (bacteriome and virome) in healthy and asthmatic individuals, including virome structure (diversity, evenness, abundance), biological function, genetic composition (nucleotide odds ratios, GC content and codon usage) and phage integration into bacterial genomes, 2) use longitudinal data to evaluate metagenome changes in time and attempt assessment of causality in relation to disease activity and 3) characterize the viral-bacterial interaction network, including host-specificity relationships, as an anticipated driver of ecological balance. CURE will thus conduct the largest and most complete metagenomic analysis of the respiratory tract undertaken to date.
CURE has a clearly foundational character with the potential to signal a new era in asthma management, followed by extensive clinical trials and research around stratification/personalisation. It would impact on respiratory medicine/allergy, providing opportunities to explore the CURE approach in several other high-burden, chronic inflammatory and possibly dysbiotic conditions, such as COPD or allergic rhinitis. Most importantly, it will herald a new line of research using phage intervention, far beyond the ‘antibiotic’ aspect, with enormous medical and industrial potential, based on an innovative microecological paradigm. This approach may expand towards more complex microbiome niches such as the gut, exploding its potential.