Faecal microbiota transplant ameliorates gut dysbiosis and cognitive deficits in Huntington’s disease mice
Open accessAbstract
Huntington’s disease is a neurodegenerative disorder involving psychiatric, cognitive and motor symptoms. Huntington’s disease is caused by a tandem-repeat expansion in the huntingtin gene, which is widely expressed throughout the brain and body, including the gastrointestinal system. There are currently no effective disease-modifying treatments available for this fatal disorder. Despite recent evidence of gut microbiome disruption in preclinical and clinical Huntington’s disease, its potential as a target for therapeutic interventions has not been explored. The microbiota–gut–brain axis provides a potential pathway through which changes in the gut could modulate brain function, including cognition. We now show that faecal microbiota transplant (FMT) from wild-type into Huntington’s disease mice positively modulates cognitive outcomes, particularly in females. In Huntington’s disease male mice, we revealed an inefficiency of FMT engraftment, which is potentially due to the more pronounced changes in the structure, composition and instability of the gut microbial community, and the imbalance in acetate and gut immune profiles found in these mice. This study demonstrates a role for gut microbiome modulation in ameliorating cognitive deficits modelling dementia in Huntington’s disease. Our findings pave the way for the development of future therapeutic approaches, including FMT and other forms of gut microbiome modulation, as potential clinical interventions for Huntington’s disease.
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FMT is ineffective in ameliorating gut dysfunction and motor functions of R6/1 mice.
“However, FMT is ineffective in ameliorating gut dysfunction and motor functions of R6/1 mice.244”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [244]
Male R6/1 mice exhibit greater resistance to FMT engraftment from wild-type mice than female R6/1 mice.
“A recent study performed FMT from WT mice into R6/1 mice and found that male R6/1 mice exhibited greater resistance to FMT engraftment when compared to female R6/1 mice.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [244]
After FMT, cognitive function of male R6/1 mice shows no discernible improvement compared with female R6/1 mice.
“Consequently, the cognitive function of male R6/1 mice showed no discernible improvement as compared to their female counterparts.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [244]
In the R6/1 HD mouse model, male R6/1 mice exhibited greater resistance to FMT engraftment when compared to female R6/1 mice.
“This phenomenon is exemplified in the R6/1 HD mouse model, wherein male R6/1 mice exhibited greater resistance to FMT engraftment when compared to female R6/1 mice.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [244]
The extent of FMT engraftment in recipient mice may be influenced by the gender of the recipients.
“In addition, the extent of FMT engraftment in recipient mice may be influenced by the gender of the recipients.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [244]
Consequently, the cognitive function of male R6/1 mice showed no discernible improvement as compared to their female counterparts.
“Consequently, the cognitive function of male R6/1 mice showed no discernible improvement as compared to their female counterparts.244”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [244]
FMT from wild-type mice into a mouse model of Huntington's disease improves cognitive outcomes, particularly in females.
“FMT from wild-type mice into a mouse model of Huntington’s disease improved cognitive outcomes, particularly in females (504).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [504]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
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- Authors
- 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., Lê Cao, K. A., Rogers, G. B., & Hannan, A. J.
- Affiliations
- The University of Melbourne (AU)
- Flinders University (AU)
- Melbourne Integrative Genomics, School of Mathematics and Statistics, University of Melbourne , Parkville, VIC 3010 , Australia
- Corresponding author
- Gubert, Carolina
- Hannan, Anthony J
- ORCID
- Venue
- Brain Communications
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-07-04
- Volume
- 4
- Issue
- 4
- Pages
- fcac205-fcac205
- ISSN
- 2632-1297 (ISSN-L)
- PMC
- PMC9400176
- OpenAlex
- W4290998841
- Cited by
- 71
- References
- 57
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 21 · 2023: 12 · 2022: 1
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- National Health and Medical Research Council
- NHMRC (GNT1136529, GNT1117148, GNT1159458, APP1155179)
- Chinese Scholarship Council
- 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, cognitive impairment, microbiota-gut-brain axis, gut microbiota, sex differences, acetate, huntingtin gene, neurodegeneration, dementia
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