Towards a gut-lung axis role in pwCF on CFTR modulators: rationale, clinical evidence and perspectives

Recent data support the existence of a "gut-lung axis" (GLA), yet it's role in chronic respiratory diseases, like cystic fibrosis (CF), is under investigation. In this review we explore the potential linkages and underlying mechanisms for gut-lung interaction axis, in terms of rationale (same embryonic and anatomical origins), microbial and immune interactions, and recent advances on GLA role in chronic lung diseases, with a focus on GLA research relevant to CF. The introduction of CFTR modulators has revolutionized CF management, dramatically reshaping the disease's clinical course by improving ion transport, mucosal hydration and mucociliary clearance. CFTR modulators are known to improve anion channel function, which has resulted in physiological and microbiological changes to the respiratory tract and gastrointestinal tract, which are likely to impact the GLA and are explored in this review. While there is a growing literature for the role of the GLA in regulating lung physiology in health and disease, additional work is warranted to elucidate molecular mechanisms by which the GLA mediates pathogenesis of disease. The ultimate goal would be to apply mechanistic understanding from the bench to the bedside to enable more personalized treatment strategies that both guide and improve lung disease management, especially in the CF field.