CFTR dysregulation drives active selection of the gut microbiome.

Autor: Stacey M Meeker, Kevin S Mears, Naseer Sangwan, Mitchell J Brittnacher, Eli J Weiss, Piper M Treuting, Nicholas Tolley, Christopher E Pope, Kyle R Hager, Anh T Vo, Jisun Paik, Charles W Frevert, Hillary S Hayden, Lucas R Hoffman, Samuel I Miller, Adeline M Hajjar
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: PLoS Pathogens, Vol 16, Iss 1, p e1008251 (2020)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1008251
Popis: 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.
Databáze: Directory of Open Access Journals
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