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Publication : CFTR dysregulation drives active selection of the gut microbiome.

First Author  Meeker SM Year  2020
Journal  PLoS Pathog Volume  16
Issue  1 Pages  e1008251
PubMed ID  31961914 Mgi Jnum  J:290660
Mgi Id  MGI:6436722 Doi  10.1371/journal.ppat.1008251
Citation  Meeker SM, et al. (2020) CFTR dysregulation drives active selection of the gut microbiome. PLoS Pathog 16(1):e1008251
abstractText  Patients with cystic fibrosis (CF) have altered fecal microbiomes compared to those of healthy controls. The magnitude of this dysbiosis correlates with measures of CF gastrointestinal (GI) disease, including GI inflammation and nutrient malabsorption. However, whether this dysbiosis is caused by mutations in the CFTR gene, the underlying defect in CF, or whether CF-associated dysbiosis augments GI disease was not clear. To test the relationships between CFTR dysfunction, microbes, and intestinal health, we established a germ-free (GF) CF mouse model and demonstrated that CFTR gene mutations are sufficient to alter the GI microbiome. Furthermore, flow cytometric analysis demonstrated that colonized CF mice have increased mesenteric lymph node and spleen TH17+ cells compared with non-CF mice, suggesting that CFTR defects alter adaptive immune responses. Our findings demonstrate that CFTR mutations modulate both the host adaptive immune response and the intestinal microbiome.
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