Pilot 11: Lung and gastrointestinal homeostasis in a germ-free CF mouse model

P.I.: Lynn Hajjar, DVM, PhD
Research Associate Professor
Comparative Medicine

Piper Treuting, DVM, MS
Associate Professor
Comparative Medicine

Cystic fibrosis (CF) results in inflammatory changes not just in the lungs but also in the gastrointestinal (GI) tract. It is not known, however, whether it is mutated CFTR or altered microbiota that plays a larger role in inflammation in CF. Two non-mutually exclusive pathways include a direct pathway, where CFTR mutation induces inflammation directly independent of microbiota, and an indirect pathway, where dysbiosis of the microbiota due to CFTR mutation results in inflammation. Using our newly derived CFTR-deficient mice that are germ-free (GF, i.e. devoid of all microbial life) we propose to differentiate these two pathways. We will identify any pathological consequences of lack of CFTR in the lungs and GI tract of GF CF mice as a measure of direct inflammation, without the confounding effects of innate and adaptive immune responses to commensal microbiota. In addition, colonization of GF CF or WT mice with CF or control microbiota will reveal the indirect pathway. Together, these experiments will demonstrate whether one pathway is dominant or whether both are active.