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Faecal microbiota transplant ameliorates gut dysbiosis and cognitive deficits in Huntington's disease mice

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posted on 2024-07-11, 02:43 authored by Carolina Gubert, Jocelyn M Choo, Chloe LoveChloe Love, Saritha Kodikara, Bethany A Masson, Jamie JM Liew, Yiwen Wang, Geraldine Kong, Vinod K Narayana, Thibault Renoir, Kim-Anh Le Cao, Geraint B Rogers, Anthony J Hannan
Abstract 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.

History

Journal

Brain Communications

Volume

4

Article number

fcac205

Pagination

1-18

Location

Oxford, Eng.

Open access

  • Yes

ISSN

2632-1297

eISSN

2632-1297

Language

English

Publication classification

C1.1 Refereed article in a scholarly journal

Issue

4

Publisher

Oxford University Press