Cftr deletion in mouse epithelial and immune cells differentially influence the intestinal microbiota
Cystic fibrosis (CF) is a life-threatening genetic disorder, caused by mutations in the CF transmembrane-conductance regulator gene (cftr) that encodes CFTR, a cAMP-activated chloride and bicarbonate channel. Clinically, CF lung disease dominates the adult patient population. However, its gastrointestinal illness claims the early morbidity and mortality, manifesting as intestinal dysbiosis, inflammation and obstruction. As CF is widely accepted as a disease of epithelial dysfunction, it is unknown whether CFTR loss-of-function in immune cells contributes to these clinical outcomes. Using cftr genetic knockout and bone marrow transplantation mouse models, we performed 16S rRNA gene sequencing of the intestinal microbes. Here we show that cftr deletion in both epithelial and immune cells collectively influence the intestinal microbiota. However, the immune defect is a major factor determining the dysbiosis in the small intestine, while the epithelial defect largely influences that in the large intestine. This finding revises the current concept by suggesting that CF epithelial defect and immune defect play differential roles in CF intestinal disease.
Scull, Callie E.; Luo, Meng; Jennings, Scott; Taylor, Christopher M.; and Wang, Guoshun, "Cftr deletion in mouse epithelial and immune cells differentially influence the intestinal microbiota" (2022). School of Medicine Faculty Publications. 445.