Document Detail


Cystic fibrosis transmembrane conductance regulator knockout mice exhibit aberrant gastrointestinal microbiota.
MedLine Citation:
PMID:  23060053     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The composition of the gastrointestinal microbiome is increasingly recognized as a crucial contributor to immune and metabolic homeostasis-deficiencies in which are characteristic of cystic fibrosis (CF) patients. The murine model (CFTR (-/-) , CF), has, in previous studies, demonstrated characteristic CF gastrointestinal (GI) manifestations including slowed transit and significant upregulation of genes associated with inflammation. To determine if characteristics of the microbiome are associated with these phenotypes we used a phylogenetic microarray to compare small intestine bacterial communities of wild type and congenic CF mice. Loss of functional CFTR is associated with significant decreases in GI bacterial community richness, evenness and diversity and reduced relative abundance of putative protective species such as Acinetobacter lwoffii and a multitude of Lactobacilliales members. CF mice exhibited significant enrichment of Mycobacteria species and Bacteroides fragilis, previously associated with GI infection and immunomodulation. Antibiotic administration to WT and CF animals resulted in convergence of their microbiome composition and significant increases in community diversity in CF mice. These communities were characterized by enrichment of members of the Lactobacillaceae and Bifidobacteriaceae and reduced abundance of Enterobacteriaceae and Clostridiaceae. These data suggest that Enterobacteria and Clostridia species, long associated with small intestinal overgrowth and inflammatory bowel disease, may suppress both ileal bacterial diversity and the particular species which maintain motility and immune homeostasis in this niche. Thus, these data provide the first indications that GI bacterial colonization is strongly impacted by the loss of functional CFTR and opens up avenues for alternative therapeutic approaches to improve CF disease management.
Authors:
Susan V Lynch; Katherine C Goldfarb; Yvette K Wild; Weidong Kong; Robert C De Lisle; Eoin L Brodie
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-10-12
Journal Detail:
Title:  Gut microbes     Volume:  4     ISSN:  1949-0984     ISO Abbreviation:  Gut Microbes     Publication Date:    2013 Jan-Feb
Date Detail:
Created Date:  2013-01-24     Completed Date:  2013-07-03     Revised Date:  2014-04-24    
Medline Journal Info:
Nlm Unique ID:  101495343     Medline TA:  Gut Microbes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  41-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacteria / classification,  genetics
Bacterial Load
Biodiversity
Biota*
Cystic Fibrosis / microbiology,  pathology
Cystic Fibrosis Transmembrane Conductance Regulator / deficiency*,  genetics
Disease Models, Animal
Female
Gastrointestinal Tract / microbiology*
Male
Mice
Mice, Knockout
Microarray Analysis
Grant Support
ID/Acronym/Agency:
AI-083479/AI/NIAID NIH HHS; T32 DK007762/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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