Influences of epithelial defect and immune defect on intestinal microbiota in cystic fibrosis

Intestinal dysbiosis is one of the major manifestations in patients with cystic fibrosis (CF). As CF is commonly accepted as an epithelial dysfunction, it is unknown whether CFTR loss-of-function in immune cells contributes to the disease pathogenesis. The goal of this study is to determine if CF immune defect facilitates CF intestinal dysbiosis, as a strategy to confirm the immune involvement in CF disease. Whole-body CF (Pan-CF), myeloid CF (Mye-CF), macrophage CF (Mac-CF), and neutrophil CF (Neu-CF) mice were established and co-housed with wild-type (WT) mice. Microbiomes in feces and intestinal contents were interrogated by 16S rRNA gene sequencing. Alpha and beta diversities were evaluated to compare their differences within each genotype and across the genotypes. Moreover, Pan-CF and WT mice with bone marrow replacement were similarly investigated for their changes in intestinal microbiota. Our data clearly demonstrate differential roles of the epithelial defect and the immune defect in CF.