Until a few years ago, the lungs of healthy individuals were considered to be sterile. Recently, it has become clear that a broad collection of microorganisms is present (termed the lung microbiome) and that changes in the lung microbiome are associated with various respiratory infections, including in patients with cystic fibrosis and pneumonia. However, it is currently unclear whether these microorganisms influence the infection process of respiratory pathogens and could be exploited to treat respiratory infections. In particular, the proposed research project aims at investigating the anti-inflammatory and anti-virulence potential of a number of lung microbiome members in order to identify health-promoting bacterial species as lung-specific probiotics. A combination of preliminary data from the host laboratory (LPM) and available literature supports the presence of beneficial bacteria in the lung microbiome. Lung microbiome members that target virulence and/or pro-inflammatory properties of the major respiratory pathogen Pseudomonas aeruginosa will be the focus. State-of-the-art in vitro and in vivo model systems that are highly relevant for the acute and chronic infection process of P. aeruginosa will be used to identify beneficial lung microbiome members and to unveil the mode of action. This project could lead to much-needed solutions to tackle the lack of effective treatments against P. aeruginosa.