A Randomized Controlled Trial of Probiotics Targeting Gut Dysbiosis in Huntington’s Disease

Article type: Research Article

Authors: Wasser, Cory I.^a | Mercieca, Emily-Clare^a | Kong, Geraldine^b | Hannan, Anthony J.^{b; c} | Allford, Brianna^a | McKeown, Sonja J.^{d; e} | Stout, Julie C.^a | Glikmann-Johnston, Yifat^{a; *}

Affiliations: [a] Turner Institute for Brain and Mental Health, Ageing and Neurodegeneration Program, School of Psychological Sciences, Monash University, Clayton, VIC, Australia | [b] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne Brain Centre, Parkville, VIC, Australia | [c] Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, Australia | [d] Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia | [e] Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

Correspondence: [*] Correspondence to: Yifat Glikmann-Johnston, Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC 3800, Australia. E-mail: yifat.glikmann-johnston@monash.edu.

Abstract: Background:Gastrointestinal symptoms are clinical features of Huntington’s disease (HD), which adversely affect people’s quality of life. We recently reported the first evidence of gut dysbiosis in HD gene expansion carriers (HDGECs). Here, we report on a randomized controlled clinical trial of a 6-week probiotic intervention in HDGECs. Objective:The primary objective was to determine whether probiotics improved gut microbiome composition in terms of richness, evenness, structure, and diversity of functional pathways and enzymes. Exploratory objectives were to determine whether probiotic supplementation improved cognition, mood, and gastrointestinal symptoms. Methods:Forty-one HDGECs, including 19 early manifest and 22 premanifest HDGECs were compared with 36 matched-healthy controls (HCs). Participants were randomly assigned probiotics or placebo and provided fecal samples at baseline and 6-week follow-up, which were sequenced using 16S-V3-V4 rRNA to characterize the gut microbiome. Participants completed a battery of cognitive tests and self-report questionnaires measuring mood and gastrointestinal symptoms. Results:HDGECs had altered gut microbiome diversity when compared to HCs, indicating gut dysbiosis. Probiotic intervention did not ameliorate gut dysbiosis or have any effect on cognition, mood, or gastrointestinal symptoms. Gut microbiome differences between HDGECs and HCs were unchanged across time points, suggesting consistency of gut microbiome differences within groups. Conclusion:Despite the lack of probiotic effects in this trial, the potential utility of the gut as a therapeutic target in HD should continue to be explored given the clinical symptomology, gut dysbiosis, and positive results from probiotics and other gut interventions in similar neurodegenerative diseases.

Keywords: Huntington’s disease, randomized controlled trial, neurodegenerative disease, gut microbiome, cognitive impairment, gut–brain axis

DOI: 10.3233/JHD-220556

Journal: Journal of Huntington's Disease, vol. 12, no. 1, pp. 43-55, 2023