Gene-Environment-Gut Interactions in Huntington's Disease Mice Are Associated with Environmental Modulation of the Gut Microbiome

Abstract

Gut dysbiosis in Huntington's disease (HD) mice has been recently uncovered using microbiome profiling in R6/1 HD mice, which has been replicated in clinical HD. It was previously found that environmental enrichment (EE) and exercise (EX) had therapeutic impacts on the brain, and associated symptoms, of these HD mice. We hypothesized that these interventions modulate the gut microbiome, configuring one of the mechanisms mediating their beneficial effects observed in HD. We therefore exposed R6/1 mice to a protocol of either EE or EX, relative to standard-housed control conditions, prior to the onset of gut dysbiosis and motor deficits, characterizing gut function, as well as gut microbiome profiling using 16S rRNA sequencing. Our multivariate analysis identified the orders Bacteroidales, Lachnospirales and Oscillospirales as the main bacterial signatures that discriminate the housing conditions. Our findings suggest a promising role for the gut microbiome in mediating the therapeutic effects of EE and EX in HD, and possibly other disorders.