Gut-Lung axis in Cystic Fibrosis: pathophysiological basis for diagnostic and therapeutic approaches

In the era of CFTR-modulator therapies, respiratory disease remains central for patients with CF, yet unresolved questions persist regarding the unpredictable onset of initial lung infections and persistent inflammation not fully addressed by CFTR function restoration. Moreover, the microbiological diagnosis poses significant challenges in reliably predicting the burden of infection. Hence, there is an urgent need for new knowledge to inform pathogenesis for new diagnostic and therapeutic approaches.

This project adopts an innovative approach to CF by exploring how organs remote from the lungs impact the disease. Emerging data suggest a link between gut microbiology, immunology, and respiratory outcomes. However, mechanisms of gut-lung cross-talk in CF have been largely ignored so far. In addition and before the onset of pulmonary pathology, pwCF experiences gastrointestinal complications that impact the quality of life. Whether, how, and to what extent the early and severe gut pathology influences lung disease remains unclear. The project aims to establish the existence of a gut-lung axis, providing evidence that the microbiological and immunological status of the gut affects lung biology and function. Exploring a new CF mouse model and gastrointestinal Pseudomonas aeruginosa infection, the project seeks to determine whether gut disease and the loss of barrier integrity lead to: 1) microbial translocation from the gut to the lung 2) airway inflammatory response and, if so, understanding how this process occurs. These efforts provide crucial insights into the influence of extrapulmonary manifestations on lung pathology and generate novel hypotheses for gut-targeted diagnostic and therapeutic approaches.