Cystic Fibrosis (CF) is a genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is the most common autosomal recessive disorder affecting Caucasians (Jackson and Goss, 2018). The disease affects >30,000 patients in the US and >70,000 patients worldwide with approximately 1000 new cases diagnosed each year.. CFTR Dysregulation Drives Active Selection of the Gut Microbiome

Patients with cystic fibrosis (CF) have been shown to have an altered gastrointestinal microbiome compared to healthy controls. While there is increasing evidence that changes in the gastrointestinal microbiome may influence CF disease, it is difficult to determine the causes and direct results of these microbiome changes in human populations as there are often a number of confounding variables. We therefore sought to establish and characterize a germ free (GF) mouse model of CF that could be used to study complex interactions between CF patient genetics and the microbiome. Our findings demonstrate that mutations in the CFTR gene are sufficient to modulate the gut microbiome. Furthermore, flow cytometric analysis performed on GF and colonized CF and nonCF mice demonstrated that CF mice have an increased number of TH17+ cells in the MLN in the absence and presence of gastrointestinal bacteria suggesting that defects in the CFTR gene modulate the adaptive immune response even in the absence of bacterial stimulation. Together our findings demonstrate that mutations in the CFTR gene modulate the host adaptive immune response and the gut microbiome. The GF CF mouse model will be a useful tool to further dissect the complex interactions between the gut microbiome and disease pathogenesis in CF.