Time-Resolved Phageomics: Assessing the potential of phage therapy in allergy and asthma. Asthma-related bacterial pathogens

Chronic respiratory diseases, such as asthma, are leading health problems of the 21st century. Viral and particularly rhinoviral infections are a major trigger of exacerbations, also promoting airway remodeling and disease persistence. However, the current state-of-the-art suggests that the whole microbiome, rather than a single microorganism, is widely disturbed in asthma, bringing forward the potential of the microbiome as a treatment target. Yet, microbiome studies have largely focused on bacteria. Pioneering the study of the respiratory virome in asthma, we have previously discovered that children with asthma have a characteristically dysbiotic virome that correlates to disease severity and control. A major component of such dysbiosis is bacteriophage deficiency, while eukaryotic viral presence is increased. Recently, we have also identified longitudinal instability, as a key characteristic of airway microbiome dysbiosis in asthma.To take an important step further, in T-ReP we hypothesize that phage deficiency is present across asthma phenotypes, and that phage-bacteria ecological equilibrium follows predator-prey cycles, which can be shifted by lysogeny. The aim of T-ReP is to quantify phageome variation and phage-bacteria interaction according to phenotype and time, and isolate phages of therapeutic relevance. To achieve this goal, we will (i) describe the characteristics of the respiratory phageome in different asthma phenotypes, (ii) investigate phageome temporal changes in health and asthma, in relation to disease activity, (iii) identify and explore phage-bacterial and phage-viral interaction networks, and (iv) isolate and characterize novel bacteriophages with therapeutic potential in asthma. This is a highly ambitious, high-risk-high-gain, yet feasible, project. Aspiring to understand mechanisms translatable into a completely new treatment approach, it is likely to have a huge impact towards science and society.