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Huntington\u2019s 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\u2019s disease, its potential as a target for therapeutic interventions has not been explored. The microbiota\u2013gut\u2013brain 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\u2019s disease mice positively modulates cognitive outcomes, particularly in females. In Huntington\u2019s 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\u2019s 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\u2019s disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac205","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T22:17:50Z","timestamp":1660256270000},"source":"Crossref","is-referenced-by-count":72,"title":["Faecal microbiota transplant ameliorates gut dysbiosis and cognitive deficits in Huntington\u2019s disease mice"],"prefix":"10.1093","volume":"4","author":[{"given":"Carolina","family":"Gubert","sequence":"first","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn M","family":"Choo","sequence":"additional","affiliation":[{"name":"Microbiome and Host Health, South Australian Health and Medical Research Institute , Adelaide, SA 5001 , Australia"},{"name":"Infection and Immunity, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University , Bedford Park, SA 5042 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe J","family":"Love","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saritha","family":"Kodikara","sequence":"additional","affiliation":[{"name":"Melbourne Integrative Genomics, School of Mathematics and Statistics, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany A","family":"Masson","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie J M","family":"Liew","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Melbourne Integrative Genomics, School of Mathematics and Statistics, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine","family":"Kong","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod K","family":"Narayana","sequence":"additional","affiliation":[{"name":"Bio21 Institute and Department of Biochemistry and Molecular Biology, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Renoir","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim Anh","family":"L\u00ea Cao","sequence":"additional","affiliation":[{"name":"Melbourne Integrative Genomics, School of Mathematics and Statistics, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraint B","family":"Rogers","sequence":"additional","affiliation":[{"name":"Microbiome and Host Health, South Australian Health and Medical Research Institute , Adelaide, SA 5001 , Australia"},{"name":"Infection and Immunity, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University , Bedford Park, SA 5042 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7532-8922","authenticated-orcid":false,"given":"Anthony J","family":"Hannan","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne , Parkville, VIC 3010 , Australia"},{"name":"Department of Anatomy and Neuroscience, University of Melbourne , Parkville, VIC 3010 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,12]]},"reference":[{"issue":"4","key":"2022082410473093800_fcac205-B1","doi-asserted-by":"crossref","first-page":"48109","DOI":"10.1007\/s11910-017-0739-9","article-title":"Huntington\u2019s disease\u2014Update on 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