CFTR dysregulation drives active selection of the gut microbiome

Autoři: Stacey M. Meeker aff001;  Kevin S. Mears aff001;  Naseer Sangwan aff002;  Mitchell J. Brittnacher aff003;  Eli J. Weiss aff003;  Piper M. Treuting aff001;  Nicholas Tolley aff001;  Christopher E. Pope aff004;  Kyle R. Hager aff003;  Anh T. Vo aff003;  Jisun Paik aff001;  Charles W. Frevert aff001;  Hillary S. Hayden aff003;  Lucas R. Hoffman aff003;  Samuel I. Miller aff003;  Adeline M. Hajjar aff001
Působiště autorů: Department of Comparative Medicine, University of Washington, Seattle, WA, United States of America aff001;  Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America aff002;  Department of Microbiology, University of Washington, Seattle, WA, United States of America aff003;  Department Pediatrics, University of Washington, Seattle, WA, United States of America aff004;  Departments of Medicine, Allergy and Infectious Disease, and Department of Genome Sciences, University of Washington, Seattle, WA, United States of America aff005;  Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America aff006
Vyšlo v časopise: CFTR dysregulation drives active selection of the gut microbiome. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008251
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008251


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.

Klíčová slova:

Body weight – Cystic fibrosis – Diet – Gastrointestinal tract – Microbiome – Mouse models – Spleen – T cells


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