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There are currently no approved disease\u2010modifying therapies available for HD, with death usually occurring approximately 10\u201325\u2009years after onset, but some therapies hold promising potential. HD subjects are often burdened by chronic diarrhea, constipation, esophageal and gastric inflammation, and a susceptibility to diabetes. Our understanding of the microbiota\u2013gut\u2013brain axis in HD is in its infancy and growing evidence from preclinical and clinical studies suggests a role of gut microbial population imbalance (gut dysbiosis) in HD pathophysiology. The gut and the brain can communicate through the enteric nervous system, immune system, vagus nerve, and microbiota\u2010derived\u2010metabolites including short\u2010chain fatty acids, bile acids, and branched\u2010chain amino acids. This review summarizes supporting evidence demonstrating the alterations in bacterial and fungal composition that may be associated with HD. We focus on mechanisms through which gut dysbiosis may compromise brain and gut health, thus triggering neuroinflammatory responses, and further highlight outcomes of attempts to modulate the gut microbiota as promising therapeutic strategies for HD. Ultimately, we discuss the dearth of data and the need for more longitudinal and translational studies in this nascent field. We suggest future directions to improve our understanding of the association between gut microbes and the pathogenesis of HD, and other \u2018brain and body disorders\u2019.<\/jats:p>","DOI":"10.1111\/febs.17102","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T09:35:06Z","timestamp":1709285706000},"page":"1282-1315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["The microbiota\u2013gut\u2013brain axis\u00a0in Huntington's disease: pathogenic mechanisms and therapeutic targets"],"prefix":"10.1111","volume":"292","author":[{"given":"Millicent N.","family":"Ekwudo","sequence":"first","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne  Parkville Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Gubert","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and 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