Intestinal dysbiosis and inflammation in cystic fibrosis impacts gut and multi-organ axes

Cystic fibrosis (CF) is a multisystem genetic disease which affects numerous organs in the body. Patients with CF exhibit profound alterations in the gastrointestinal microbiome, characterised by an increase in pathogenic bacteria and reduction in beneficial commensal species, accompanied by intestinal inflammation. The proposed pathophysiology of these gastrointestinal changes is multifactorial, driven primarily by dysfunction of the CF transmembrane conductance regulator (CFTR) protein, and secondarily by medications and the high-fat CF diet. Increasingly, the gastrointestinal microbiome is being recognised as an endocrine-like organ which regulates the function of multiple organs via direct transmission of microbes and metabolites, inflammatory pathways, immunological crosstalk, and other mechanisms. This article aims to review how the gut microbiome in CF may influence other affected organs, including the intestines, lungs (gut-lung axis), liver (gut-liver axis), bones (gut-bone axis), pancreas (gut-pancreas axis), and brain (gut-brain axis). Further research is required to better understand the potential role of the gut microbiome in CF multisystem disease, and the therapeutic utility of gut and multi-organ axes in CF.