CFTR dysregulation drives active selection of the gut microbiome.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
08
07
2019
accepted:
05
12
2019
revised:
31
01
2020
pubmed:
22
1
2020
medline:
6
5
2020
entrez:
22
1
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31961914
doi: 10.1371/journal.ppat.1008251
pii: PPATHOGENS-D-19-01215
pmc: PMC6994172
doi:
Substances chimiques
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008251Subventions
Organisme : NIH HHS
ID : K01 OD021420
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL141669
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK017047
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK089507
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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