CoChat
Sign Up
Cited by 212Gut microbiota and healthGenetic Neurodegenerative DiseasesGastrointestinal motility and disorders

The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.

Microbiome profiling reveals gut dysbiosis in a transgenic mouse model of Huntington's disease

Open access
Kong, Geraldine, Cao, Kim-Anh Lê, Judd, Louise M., Li, ShanShan, Renoir, Thibault, Hannan, Anthony J.·2020·Neurobiology of Disease
DOI 10.1016/j.nbd.2018.09.001
Open this paper in CoChat — free accountOpen PDF

Abstract

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a trinucleotide repeat expansion in the huntingtin (HTT) gene, which is expressed ubiquitously throughout the brain and peripheral tissues. Whilst the focus of much research has been on the cognitive, psychiatric and motor symptoms of HD, the extent of peripheral pathology and its potential impact on central symptoms has been less intensely explored. Disruption of the gastrointestinal microbiome (gut dysbiosis) has been recently reported in a number of neurological and psychiatric disorders, and therefore we hypothesized that it might also occur in HD. We have used 16S rRNA amplicon sequencing to characterize the gut microbiome in the R6/1 transgenic mouse model of HD, relative to littermate wild-type controls. We report that there is a significant difference in microbiota composition in HD mice at 12 weeks of age. Specifically, we observed an increase in Bacteriodetes and a proportional decrease in Firmicutes in the HD gut microbiome. In addition, we observed an increase in microbial diversity in male HD mice, compared to wild-type controls, but no differences in diversity were observed in female HD mice. The gut dysbiosis observed coincided with impairment in body weight gain despite higher food intake as well as motor deficits at 12 weeks of age. Gut dysbiosis was also associated with a change in the gut microenvironment, as we observed higher fecal water content in HD mice at 12 weeks of age. This study provides the first evidence of gut dysbiosis in HD.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.nbd.2018.09.001

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Figures

Image 1
CC-BY-NC-ND · From the PDF
Fig. 1 Percentage of weight gain in R6/1 mice. (A) Male HD mice had decreased percentage of weight gain compared to WT, whereas there were no differences in weight gain in (B) female HD and WT. Data represents mean percentage of weight gain normalized to body weight at 5 weeks of age ± standard error mean (SEM) (** p < 0.005, *** p < 0.0005; n =7-11).
Fig. 1 Percentage of weight gain in R6/1 mice. (A) Male HD mice had decreased percentage of weight gain compared to WT, whereas there were no differences in weight gain in (B) female HD and WT. Data represents mean percentage of weight gain normalized to body weight at 5 weeks of age ± standard error mean (SEM) (** p < 0.005, *** p < 0.0005; n =7-11).CC-BY-NC-ND · From the PDF
Fig. 2 (A) Food intake and (B) water intake of WT and HD mice at 12 weeks of age. Male HD mice had significantly higher food and water intake compared to WT mice at 12 weeks of age. Female HD were drinking more at 12 weeks of age compared to WT. Data represent average food and water intake per g of body weight ± SEM. (* p < 0.05, ** p < 0.01, n = 7-11 mice).
Fig. 2 (A) Food intake and (B) water intake of WT and HD mice at 12 weeks of age. Male HD mice had significantly higher food and water intake compared to WT mice at 12 weeks of age. Female HD were drinking more at 12 weeks of age compared to WT. Data represent average food and water intake per g of body weight ± SEM. (* p < 0.05, ** p < 0.01, n = 7-11 mice).CC-BY-NC-ND · From the PDF
Fig. 3 (A,B) Fecal output and (C,D) fecal water content of WT and HD mice from 8 to 12 weeks of age. There was a significant main effect of genotype on the fecal output in males but no significant differences were found in the females. For fecal water content, there was a significant main effect of genotype observed in the females but not in the males. Values represent means ± SEM (*p < 0.05, n = 7-11 mice).
Fig. 3 (A,B) Fecal output and (C,D) fecal water content of WT and HD mice from 8 to 12 weeks of age. There was a significant main effect of genotype on the fecal output in males but no significant differences were found in the females. For fecal water content, there was a significant main effect of genotype observed in the females but not in the males. Values represent means ± SEM (*p < 0.05, n = 7-11 mice).CC-BY-NC-ND · From the PDF
Fig. 4 Principal coordinate analysis of male and female data using Bray-Curtis distance with different combinations of metadata shown: A) genotype and sex, B) genotype and cage. Amount of explained variance per component is reported. The samples clustered according to sex as well as genotype, and to some extent, to cage. There were significant differences between the two genotypes for both sexes on the Bray-Curtis distance. No significant sex differences on Bray-Curtis distance but they were significant on the unweighted UniFrac distance (not shown here) (n = 7-8).
Fig. 4 Principal coordinate analysis of male and female data using Bray-Curtis distance with different combinations of metadata shown: A) genotype and sex, B) genotype and cage. Amount of explained variance per component is reported. The samples clustered according to sex as well as genotype, and to some extent, to cage. There were significant differences between the two genotypes for both sexes on the Bray-Curtis distance. No significant sex differences on Bray-Curtis distance but they were significant on the unweighted UniFrac distance (not shown here) (n = 7-8).CC-BY-NC-ND · From the PDF
Fig. 5 The relative abundance of the major phyla, Bacteroidetes and Firmicutes, was examined for (A) male and (C) female mice. The relative abundance of minor phyla, Actinobacteria, Deferribacteres and Proteobacteria, was also examined for (B) male and (D) female mice. There was a significant increase in the Bacteroidetes phylum, with significant proportional decrease in the Firmicutes phylum, in HD mice for both sexes. There were also significant differences in the proportions of the minor phyla, but this was only observed in the males. The plots show mean ± SEM (n = 7-8).
Fig. 5 The relative abundance of the major phyla, Bacteroidetes and Firmicutes, was examined for (A) male and (C) female mice. The relative abundance of minor phyla, Actinobacteria, Deferribacteres and Proteobacteria, was also examined for (B) male and (D) female mice. There was a significant increase in the Bacteroidetes phylum, with significant proportional decrease in the Firmicutes phylum, in HD mice for both sexes. There were also significant differences in the proportions of the minor phyla, but this was only observed in the males. The plots show mean ± SEM (n = 7-8).CC-BY-NC-ND · From the PDF
Fig. 6 (A) Alpha diversity metrics including Observed, Shannon and Inverse Simpson (InvSimpson) indices were probed for male and (B) female data. For male mice, there was no difference in Observed but the Shannon and Inverse Simpson indices were significantly higher in HD mice compared to WT. There were no differences in all three indices for female mice (n = 7-8).
Fig. 6 (A) Alpha diversity metrics including Observed, Shannon and Inverse Simpson (InvSimpson) indices were probed for male and (B) female data. For male mice, there was no difference in Observed but the Shannon and Inverse Simpson indices were significantly higher in HD mice compared to WT. There were no differences in all three indices for female mice (n = 7-8).CC-BY-NC-ND · From the PDF
Fig. 7 Identification of a bacterial signature discriminating the two sexes with sPLS-DA. Sample plots with 0.95 confidence ellipse plots for (A) WT and (C) HD show a strong discrimination between HD and WT. The top 20 resulting bacterial signature contributing to component 1 is displayed in (B) for WT and in (D) for HD. The length of the bars indicates the importance of each OTU (at the Order taxonomic rank) in the signature (from bottom to top: decreasing importance) with color indicating the phenotype group with maximum median abundance. The OTUs shown are at the Order taxonomic level.
Fig. 7 Identification of a bacterial signature discriminating the two sexes with sPLS-DA. Sample plots with 0.95 confidence ellipse plots for (A) WT and (C) HD show a strong discrimination between HD and WT. The top 20 resulting bacterial signature contributing to component 1 is displayed in (B) for WT and in (D) for HD. The length of the bars indicates the importance of each OTU (at the Order taxonomic rank) in the signature (from bottom to top: decreasing importance) with color indicating the phenotype group with maximum median abundance. The OTUs shown are at the Order taxonomic level.CC-BY-NC-ND · From the PDF
Fig. 8 Identification of a bacterial signature associated with HD vs WT with sPLS-DA. Sample plots with 0.95 confidence ellipse plots for (A) male and (C) female show a strong discrimination between HD and WT. The resulting bacterial signature contributing to component 1 is displayed in (B) for males and for females, the top 20 bacterial signature is displayed in (D). The length of the bars indicates the importance of each OTU in the signature (from bottom to top: decreasing importance) with color indicating the phenotype group with maximum median abundance. The OTUs shown are at the Order taxonomic level. In the case when the Order level is not assigned, the next highest level is shown.
Fig. 8 Identification of a bacterial signature associated with HD vs WT with sPLS-DA. Sample plots with 0.95 confidence ellipse plots for (A) male and (C) female show a strong discrimination between HD and WT. The resulting bacterial signature contributing to component 1 is displayed in (B) for males and for females, the top 20 bacterial signature is displayed in (D). The length of the bars indicates the importance of each OTU in the signature (from bottom to top: decreasing importance) with color indicating the phenotype group with maximum median abundance. The OTUs shown are at the Order taxonomic level. In the case when the Order level is not assigned, the next highest level is shown.CC-BY-NC-ND · From the PDF

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 60 references

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Kong, G., Cao, K.-A. L., Judd, L. M., Li, S., Renoir, T., & Hannan, A. J.
Affiliations
The University of Melbourne (AU)
Corresponding author
Hannan, Anthony J.
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2020-02
Volume
135
Pages
104268
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2018.09.001
OpenAlex
W2889638535
Cited by
212
References
60
Citations by year
2026: 13 · 2025: 35 · 2024: 39 · 2023: 27 · 2022: 37 · 2021: 32 · 2020: 20
FWCI
5.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
NHMRC (GNT1087415)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
Huntington's disease, gut dysbiosis, gut microbiota, Bacteroidetes, Firmicutes, microbial diversity, sex differences, weight gain, motor impairment, fecal water content
MeSH terms
Gastrointestinal Microbiome, Huntingtin Protein, Animals, Brain, Disease Models, Animal, Huntington Disease, Male, Mice, Transgenic, Motor Activity, Nerve Tissue Proteins, Trinucleotide Repeat Expansion, Dysbiosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review