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Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease

Stan, Tiberiu Loredan LU ; Soylu-Kucharz, Rana LU ; Burleigh, Stephen LU ; Prykhodko, Olena LU ; Cao, Ling LU ; Franke, Naomi ; Sjögren, Marie LU ; Haikal, Caroline LU ; Hållenius, Frida LU orcid and Björkqvist, Maria LU orcid (2020) In Scientific Reports 10(1).
Abstract

Huntington’s disease (HD) is a progressive, multifaceted neurodegenerative disease associated with weight loss and gut problems. Under healthy conditions, tight junction (TJ) proteins maintain the intestinal barrier integrity preventing bacterial translocation from the intestinal lumen to the systemic circulation. Reduction of TJs expression in Parkinson’s disease patients has been linked with increased intestinal permeability—leaky gut syndrome. The intestine contains microbiota, most dominant phyla being Bacteroidetes and Firmicutes; in pathogenic or disease conditions the balance between these bacteria might be disrupted. The present study investigated whether there is evidence for an increased intestinal permeability and dysbiosis... (More)

Huntington’s disease (HD) is a progressive, multifaceted neurodegenerative disease associated with weight loss and gut problems. Under healthy conditions, tight junction (TJ) proteins maintain the intestinal barrier integrity preventing bacterial translocation from the intestinal lumen to the systemic circulation. Reduction of TJs expression in Parkinson’s disease patients has been linked with increased intestinal permeability—leaky gut syndrome. The intestine contains microbiota, most dominant phyla being Bacteroidetes and Firmicutes; in pathogenic or disease conditions the balance between these bacteria might be disrupted. The present study investigated whether there is evidence for an increased intestinal permeability and dysbiosis in the R6/2 mouse model of HD. Our data demonstrate that decreased body weight and body length in R6/2 mice is accompanied by a significant decrease in colon length and increased gut permeability compared to wild type littermates, without any significant changes in the protein levels of the tight junction proteins (occludin, zonula occludens). Moreover, we found an altered gut microbiota in R6/2 mice with increased relative abundance of Bacteroidetes and decreased of Firmicutes. Our results indicate an increased intestinal permeability and dysbiosis in R6/2 mice and further studies investigating the clinical relevance of these findings are warranted.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
10
issue
1
article number
18270
publisher
Nature Publishing Group
external identifiers
  • scopus:85094200790
  • pmid:33106549
ISSN
2045-2322
DOI
10.1038/s41598-020-75229-9
language
English
LU publication?
yes
id
99213226-9833-47e3-9c45-e62046b059bc
date added to LUP
2020-11-04 13:43:43
date last changed
2025-04-18 05:05:10
@article{99213226-9833-47e3-9c45-e62046b059bc,
  abstract     = {{<p>Huntington’s disease (HD) is a progressive, multifaceted neurodegenerative disease associated with weight loss and gut problems. Under healthy conditions, tight junction (TJ) proteins maintain the intestinal barrier integrity preventing bacterial translocation from the intestinal lumen to the systemic circulation. Reduction of TJs expression in Parkinson’s disease patients has been linked with increased intestinal permeability—leaky gut syndrome. The intestine contains microbiota, most dominant phyla being Bacteroidetes and Firmicutes; in pathogenic or disease conditions the balance between these bacteria might be disrupted. The present study investigated whether there is evidence for an increased intestinal permeability and dysbiosis in the R6/2 mouse model of HD. Our data demonstrate that decreased body weight and body length in R6/2 mice is accompanied by a significant decrease in colon length and increased gut permeability compared to wild type littermates, without any significant changes in the protein levels of the tight junction proteins (occludin, zonula occludens). Moreover, we found an altered gut microbiota in R6/2 mice with increased relative abundance of Bacteroidetes and decreased of Firmicutes. Our results indicate an increased intestinal permeability and dysbiosis in R6/2 mice and further studies investigating the clinical relevance of these findings are warranted.</p>}},
  author       = {{Stan, Tiberiu Loredan and Soylu-Kucharz, Rana and Burleigh, Stephen and Prykhodko, Olena and Cao, Ling and Franke, Naomi and Sjögren, Marie and Haikal, Caroline and Hållenius, Frida and Björkqvist, Maria}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-75229-9}},
  doi          = {{10.1038/s41598-020-75229-9}},
  volume       = {{10}},
  year         = {{2020}},
}