Over 300 million patients with chronic lung diseases (CLD) worldwide need novel anti-inflammatory agents. We recently found that the lung microbiome contains beneficial anti-inflammatory bacteria that inhibit the overt pro-inflammatory response which causes impaired lung function and premature death in patients with CLD. Yet, how exactly these anti-inflammatory bacteria inhibit the detrimental pro-inflammatory host response is unknown. This project aims to address this gap by (i) identifying anti-inflammatory metabolites produced by the lung microbiome of patients with chronic lung diseases, and (ii) deciphering their mode of action. Identification of anti-inflammatory metabolites will be done using a multi-tiered, complementary approach, including using respiratory samples of patients with CLD. Hence, the clinical relevance of the findings in this project is central. It is anticipated that this project will not only fill key knowledge gaps on host-microbiome interactions that drive the inflammatory process, but will lay the foundations for a much-needed therapeutic approach against CLD.