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Dietary fibre confers therapeutic effects in a preclinical model of Huntington’s disease.
Huntington’s disease (HD) causes mental, motor, and cognitive impairments and other peripheral symptoms, including gastrointestinal problems, a clinical picture seen in neurodegenerative diseases. The R6/1 HD mouse model, which expresses a mutant human huntingtin transgene, has demonstrated that it offers a reliable model to study this condition. Recent research on preclinical and clinical HD has demonstrated alteration of the gut flora. Thus, Gubert et al. (2024) evaluated how gut microbial manipulation may be used to treat HD. From six to twenty weeks of age, the R6/1 HD mice and wild-type littermate controls were randomized to receive meals with varying quantities of fiber: high-fiber (10% fiber), control (5% fiber), or zero-fibre (0% fiber). The authors collected data on gastrointestinal function, gut morphological alterations, and the start and course of cognitive, motor, and psychological impairments. At 14 and 20 weeks of age, feces were collected for 16S rRNA sequencing gut microbiome characterization. Analysis of the results showed that, in assessments of gastrointestinal function, in addition to behavioral assessments of affective and cognitive function, both HD and wild-type mice performed better on the high-fiber diet than on the control diet. Although the diets altered the beta diversity (i.e., uniformity of microbiome composition) in wild-type mice, in HD mice, no statistically significant change was seen at 14 or 20 weeks of age. After receiving a high-fiber diet, HD mice showed differences in microbiota composition compared to wild-type mice. These differences included a decreased relative abundance of the phyla Campylobacterota, Actinobacteriota, and Proteobacteria and an increased relative abundance of the families Oscillospiraceae, Bacteroidaceae, and Ruminococcaceae. These differences were assessed using Analysis of the Composition of Microbiomes with Bias Correction (ANCOM-BC) models. High-fiber diets significantly reduced potentially harmful functional pathways in HD, according to Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2, used to forecast functional profiles of microbiome communities). In summary, feeding HD mice a high-fiber diet improved their cognition, gastrointestinal system, and emotional behaviors. The authors comment that their results suggest how dietary fiber treatments may show promise in postponing the clinical onset of Huntington’s disease and may have a further impact on other conditions involving gut-brain axis dysfunction. [NPID: Dementia, Depression, dietary fiber, gut microbiome, Huntington’s disease, microbiota-gut-brain axis, neurodegenerative disorder]
Year: 2024
