METABOLEGIO

Legionnaires’ disease (LD) is an increasing cause of community-acquired pneumonia associated with digestive symptoms and high mortality rates, particularly in intensive care patients. This project aims to address two key issues: the poorly understood pathogenesis of LD severity and the lack of prognostic biomarkers. Recent studies have shown that LD leads to a disrupted lung microbiota characterized by Legionella overgrowth, which ousts resident microbiota. Additionally, the gut-lung axis has emerged as a critical area of research, revealing how gut microbiota metabolites influence systemic host physiology. However, no studies have investigated the gut-lung axis and metabolic changes during LD. We propose to use integrative metabolomic and genomics approaches on a collection of lung, stool, urine, and blood samples from a well-characterized cohort of 120 patients. Our objectives are: (i) to investigate key metabolites produced during Legionella infection and their role in LD pathogenesis; (ii) to identify innovative metabolites as potential biomarkers for LD diagnosis and monitoring; (iii) to investigate the interactions between gut and lung microbiota, as well as their relationship with the bloodstream during Legionella infection. Our multidisciplinary consortium comprises experts in clinical microbiology, host-pathogen interactions, biochemistry, microbiota, metabolomic analyses, and genome-wide approaches. This collaborative effort aims to develop a rapid, non-invasive tool to improve LD diagnosis and monitoring, ultimately enhancing patient outcomes.