Pneumonia heterogeneity based on lung microbiota signature to predict patients at risk and treatment response

Objective

Hospital-acquired pneumonia is the second most frequent nosocomial infection in the world, leading to high mortality and morbidity. Their management is standardised and targets the dominant bacteria identified on sample culture. However, this “one-size-fits-all” approach leads to a treatment success rate that rarely goes beyond 60%, suggesting a knowledge gap in the underlying mechanisms. Recent discoveries highlighted that hospital-acquired pneumonia pathophysiology involved several actors, notably a rich and diverse respiratory microbiota with complex dynamics, that yet remains overlooked. Despite recent innovative therapies, treating pneumonia as a homogenous disease without taking into account the microbiota diversity, will lead to negative and unconclusive results. The MATRICS project aims at demonstrating, using lung microbiota signature and dynamics, that hospital-acquired pneumonia is not a homogeneous disease and should thus benefit from a tailored therapeutic strategy. The objectives of this project are: 1) To first describe lung microbiota dynamics during pneumonia, using longitudinal microbiome data from international cohorts; 2) To unveil a microbiota-based heterogeneity of pneumonia that is associated with clinical outcomes. This will lead to the development of a classification model to distinguish pneumonia patients based on their lung microbiome signature; 3) To assess the impact of a steroid-based therapy in hospital-acquired pneumonia, on lung microbiota, using data from an ongoing clinical trial and then validate the findings in vitro. Finally, I will investigate how prior microbiota-based classification of pneumonia patients can predict the clinical response to steroid therapy. The ambition of the MATRICS project is to propose a new insight in pneumonia pathophysiology that will deeply impact the therapeutic strategy towards a precision medicine. Such innovative approach could potentially extend to other respiratory diseases.