The advent of CFTR modulator drugs marked a turning point in the treatment of cystic fibrosis (CF). These drugs slow the progression of the disease, but they cannot stop it or repair existing damage, leaving residual infection and inflammation in the lungs that current tools cannot accurately predict.
CF research has focused particularly on the lungs; however, it is also important to investigate the involvement of other organs, such as those of the digestive system.
In particular, it is still unclear whether and how the gastrointestinal complications typical of CF affect infection and inflammation of the lungs: this project aimed to verify the existence of a connection between the intestine and the lungs.

To study the gut-lung dynamics, the researchers adopted a “multi-organ” approach and studied how the two organs communicate with each other. 
An animal model with the F508del mutation, which reproduces the characteristics of the human disease, was infected with Pseudomonas aeruginosa. In this model, the immune system response and the behavior of bacteria in the lungs, intestines, and blood were analyzed, and it was observed that the intestines and lungs share a population of bacteria. Furthermore, it emerged that the intestine influences the inflammatory response in the lungs.
The data obtained in vivo were then confirmed on biological samples (sputum and feces) from people with CF. The aim was to understand whether the bacteria found in the two organs were the same and how they were able to adapt to the different environments present in the lungs and intestines.
The data obtained from human biological samples showed that some bacteria typical of cystic fibrosis, such as Staphylococcus aureus and Pseudomonas aeruginosa, are present in both the respiratory tract and the intestine.
This indicates that the intestine is not an isolated compartment, but an area where bacteria can settle and influence inflammation throughout the body.

These results highlight the importance of gut-lung communication in the establishment of infection and respiratory inflammation typical of CF; they also identify the intestine as a new potential target for diagnosis and therapies, complementary to those focused on the lungs.

Publications

• Unlock the gut-lung axis in Cystic Fibrosis leveraging Collaborative Cross mice genetic diversity.
  Journal of Experimental Medicine. Under review