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

Study information

Reviewed Marked as Reviewed by Fatima on 2023/01/25

study design

randomized controlled trial

Citation

PMID PubMed identifier for scientific articles.

33106549

DOI Digital object identifier for electronic documents.

10.1038/s41598-020-75229-9

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589489/

Authors

Stan TL, Soylu-Kucharz R, Burleigh S, Prykhodko O, Cao L, Franke N, Sjögren M, Haikal C, Hållenius F, Björkqvist M

Journal

Scientific reports

Year

2020

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.

Experiment 1

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Reviewed Marked as Reviewed by Fatima on 2023/01/25

Curated date: 2022/08/22

Curator: Fatima

Revision editor(s): Fatima, Jacquelynshevin

Subjects

Location of subjects: Sweden

Host species Species from which microbiome was sampled. Contact us to have more species added.: Mus musculus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Huntington disease HD,Huntington chorea,Huntington disease,Huntington's chorea,Huntington's disease

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Wild type

Group 1 name Corresponds to the case (exposed) group for case-control studies: R6/2

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: The CAG-repeat lengths of the R6/2 mice used in this study ranged between 242 and 257, resulting in a disease progression slower than that of the R6/2 mouse with 150 CAG repeats as described previously.

Group 0 sample size Number of subjects in the control (unexposed) group: 10

Group 1 sample size Number of subjects in the case (exposed) group: 10

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): .05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2023/01/25

Curated date: 2023/01/09

Curator: Jacquelynshevin

Revision editor(s): Jacquelynshevin

Source: Figure 3 Supplemental Text

Description: Relative Abundance between wildtype and R6/2

Abundance in Group 1: increased abundance in R6/2

NCBI	Quality Control	Links
Bacilli
Bacteroidaceae
Bacteroides
Coprobacillus
Enterobacteriaceae
Gammaproteobacteria
Lactobacillales
Lactobacillus
Parabacteroides
Enterobacterales
Lactobacillaceae