Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease
Open accessAbstract
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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The HDGEC study did not observe an increase in Bacteroidetes and a reduction in Firmicutes as reported in R6/1 and R6/2 mice.
“However, the study did not observe an increase in Bacteroidetes and a reduction in Firmicutes, as reported in both R6/1 and R6/2 mice.235,236”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [236]
R6/2 mice exhibit increased intestinal permeability and reduced colon length at 16 weeks of age compared with age-matched wild-type mice.
“It was found that R6/2 mice exhibited increased intestinal permeability and reduced colon length at 16 weeks of age (early-mid disease stage), as compared to age-matched WT mice.236”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [236]
A higher relative abundance of Bacteroidetes and a lower relative abundance of Firmicutes are reported in both R6/1 and R6/2 mice compared with wild-type mice.
“Moreover, a higher relative abundance of Bacteroidetes and a lower relative abundance of Firmicutes were reported in both R6/1 and R6/2 mice, as compared to WT mice.235,236”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [236]
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- Authors
- Stan, T. L., Soylu-Kucharz, R., Burleigh, S., Prykhodko, O., Cao, L., Franke, N., Sjögren, M., Haikal, C., Hållenius, F., & Björkqvist, M.
- Affiliations
- Lund University (SE)
- Corresponding author
- Soylu-Kucharz, Rana
- ORCID
- Venue
- Scientific Reports
- Published
- 2020-10-26
- Volume
- 10
- Issue
- 1
- Pages
- 18270-18270
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7589489
- OpenAlex
- W3094034464
- Cited by
- 101
- References
- 48
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 22 · 2023: 17 · 2022: 26 · 2021: 11
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Royal Physiographic Society of Lund
- Per Westlings funds
- Knut och Alice Wallenbergs Stiftelse
- Svenska Sällskapet för Medicinsk Forskning
- The Direktör Albert Påhlsson Foundation, Sweden
- Vetenskapsrådet (#2017-01080)
- Lund University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Huntington's disease, intestinal permeability, gut dysbiosis, R6/2 mouse model, tight junction proteins, occludin, zonula occludens, gut microbiota, Bacteroidetes, Firmicutes, leaky gut, weight loss, colon length
- MeSH terms
- Gastrointestinal Microbiome, Animals, Bacteria, Body Weight, Disease Models, Animal, DNA, Bacterial, DNA, Ribosomal, Female, Humans, Huntington Disease, Male, Phylogeny, RNA, Ribosomal, 16S, Sequence Analysis, DNA, Bacterial Physiological Phenomena, Bacterial Translocation, Mice, Tight Junction Proteins, Dysbiosis
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