Gut dysbiosis in Huntington’s disease: associations among gut microbiota, cognitive performance and clinical outcomes
Open accessAbstract
Huntington’s disease is characterized by a triad of motor, cognitive and psychiatric impairments, as well as unintended weight loss. Although much of the research has focused on cognitive, motor and psychiatric symptoms, the extent of peripheral pathology and the relationship between these factors, and the core symptoms of Huntington’s disease, are relatively unknown. Gut microbiota are key modulators of communication between the brain and gut, and alterations in microbiota composition (dysbiosis) can negatively affect cognition, behaviour and affective function, and may be implicated in disease progression. Furthermore, gut dysbiosis was recently reported in Huntington’s disease transgenic mice. Our main objective was to characterize the gut microbiome in people with Huntington’s disease and determine whether the composition of gut microbiota are significantly related to clinical indicators of disease progression. We compared 42 Huntington’s disease gene expansion carriers, including 19 people who were diagnosed with Huntington’s disease (Total Functional Capacity > 6) and 23 in the premanifest stage, with 36 age- and gender-matched healthy controls. Participants were characterized clinically using a battery of cognitive tests and using results from 16S V3 to V4 rRNA sequencing of faecal samples to characterize the gut microbiome. For gut microbiome measures, we found significant differences in the microbial communities (beta diversity) based on unweighted UniFrac distance (P = 0.001), as well as significantly lower alpha diversity (species richness and evenness) between our combined Huntington’s disease gene expansion carrier group and healthy controls (P = 0.001). We also found major shifts in the microbial community structure at Phylum and Family levels, and identified functional pathways and enzymes affected in our Huntington’s disease gene expansion carrier group. Within the Huntington’s disease gene expansion carrier group, we also discovered associations among gut bacteria, cognitive performance and clinical outcomes. Overall, our findings suggest an altered gut microbiome in Huntington’s disease gene expansion carriers. These results highlight the importance of gut biomarkers and raise interesting questions regarding the role of the gut in Huntington’s disease, and whether it may be a potential target for future therapeutic intervention.
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HD gene expansion carriers have an altered gut microbiome compared with age-matched and gender-matched healthy controls.
“A recent study on HD gene expansion carriers (HDGECs) has identified an altered gut microbiome compared to age-matched and gender-matched healthy controls.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [237]
Reduced abundance of Eubacterium hallii is associated with increased severity of motor deficits in HD gene expansion carriers.
“Moreover, a reduced abundance of Eubacterium hallii was associated with increased severity of motor deficits.237”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [237]
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The microbiota–microglia axis in central nervous system disorders
Mossad, O., & Erny, D. (2020) · Brain Pathology · doi:10.1111/bpa.12908 · Cited by 98 · see citing works
Gubert, C., Choo, J. M., Love, C. J., Kodikara, S., Masson, B. A., Liew, J. J. M., Wang, Y., Kong, G., Narayana, V. K., Renoir, T., et al. (2022) · Brain Communications · doi:10.1093/braincomms/fcac205 · Cited by 71 · see citing works
Self-citationBenameur, T., Porro, C., Twfieg, M.-E., Benameur, N., Panaro, M. A., Filannino, F. M., & Hasan, A. (2023) · Brain Sciences · doi:10.3390/brainsci13081226 · Cited by 60 · see citing works
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Self-citationMetformin to treat Huntington disease: A pleiotropic drug against a multi-system disorder
Trujillo-Del Río, C., Tortajada-Pérez, J., Gómez-Escribano, A. P., Casterá, F., Peiró, C., Millán, J. M., Herrero, M. J., & Vázquez-Manrique, R. P. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111670 · Cited by 19 · see citing works
- Authors
- Wasser, C. I., Mercieca, E.-C., Kong, G., Hannan, A. J., McKeown, S. J., Glikmann-Johnston, Y., & Stout, J. C.
- Affiliations
- Monash University (AU)
- The University of Melbourne (AU)
- Ageing and Neurodegeneration Program, School of Psychological Sciences, Turner Institute for Brain and Mental Health, Monash University, Clayton, Victoria 3800, Australia
- Corresponding author
- Stout, Julie C
- ORCID
- Venue
- Brain Communications
- Publisher
- Oxford University Press (OUP)
- Published
- 2020
- Volume
- 2
- Issue
- 2
- Pages
- fcaa110-fcaa110
- ISSN
- 2632-1297 (ISSN-L)
- PMC
- PMC7519724
- OpenAlex
- W3045452138
- Cited by
- 198
- References
- 80
- Citations by year
- 2026: 23 · 2025: 37 · 2024: 44 · 2023: 35 · 2022: 38 · 2021: 18 · 2020: 3
- FWCI
- 7.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain Communications (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (submittedVersion, other-oa)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
- Funders
- Australian Government National Health
- Medical Research Council
- The Fox Family Foundation
- Torquay Coasters Cycling Group
- 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, cognitive performance, disease progression, gene expansion carriers, premanifest Huntington's disease, alpha diversity, beta diversity, gut-brain axis, fecal microbiota
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