Gene-environment-gut interactions in Huntington's disease mice are associated with environmental modulation of the gut microbiome

• Published in: iScience Vol. 25; no. 1; p. 103687
• Main Authors: Gubert, Carolina, Love, Chloe Jane, Kodikara, Saritha, Mei Liew, Jamie Jie, Renoir, Thibault, Lê Cao, Kim-Anh, Hannan, Anthony John
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.01.2022; Elsevier
• Subjects: Disease; Microbiology; Microbiome; Disease; Microbiology; Microbiome
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2021.103687

Gut dysbiosis in Huntington's disease (HD) has recently been reported using microbiome profiling in R6/1 HD mice and replicated in clinical HD. In HD mice, environmental enrichment (EE) and exercise (EX) were shown to have therapeutic impacts on the brain and associated symptoms. We hypothesize that these housing interventions modulate the gut microbiome, configuring one of the mechanisms that mediate their therapeutic effects observed in HD. We exposed R6/1 mice to a protocol of either EE or EX, relative to standard-housed control conditions, before the onset of gut dysbiosis and motor deficits. We characterized gut structure and function, as well as gut microbiome profiling using 16S rRNA sequencing. Multivariate analysis identified specific orders, namely Bacteroidales, Lachnospirales and Oscillospirales, as the main bacterial signatures that discriminate between housing conditions. Our findings suggest a promising role for the gut microbiome in mediating the effects of EE and EX exposures, and possibly other environmental interventions, in HD mice. [Display omitted] •Gastrointestinal structure and motility are intact at an early stage in a HD mouse model•There is sexual dimorphism in the presentation of the HD gut dysbiosis phenotype•Bacteroidales, Lachnospirales and Oscillospirales bacteria are affected by experience•Environmental enrichment and exercise may modulate HD via the microbiota-gut-brain axis Disease; Microbiology; Microbiome