The gut microbiota plays a key role in pulmonary defense against infection. It can distally, through metabolites and cell wall components, arm immune cells to fight infection. Elderly adults are especially vulnerable to respiratory tract infections. We hypothesize that an alteration in the gut-lung axis - caused by gut dysbiosis - is involved in this high susceptibility. Our research has shown that an old microbiota can remotely transfer susceptibility to respiratory infection. In a murine model, we will first seek to identify microbial candidates and bacterially produced metabolites involved in the age-dependent control of pulmonary defences against bacterial infections (Pneumococcus) and viral infections (influenza). This approach will be based on faecal transfer experiments, microbiota sequencing, metabolomics analyses and biostatistical and correlative analyses. For translational perspectives, potential candidates will be also identified in human samples. In recipient mice, we will determine the mechanisms underlying microbiota-mediated pulmonary immune (dys)function. Later, microbial and metabolite candidates will be used to manipulate the gut microbiota and thus better control respiratory infections in older animals. The GUTSY program is of biomedical importance.