F090 Microbiota in a Huntington disease, ENROLL-HD, cohort reveals differences across disease stages

<h3>Background</h3> Microbiota dysbiosis and imbalance of the microbial profile play a role in neurodegenerative disorders including Huntington disease (HD). <h3>Aims</h3> Investigation of difference in the gut metagenome between HD subjects and controls. <h3>Methods</h3> We enrolled 110 individuals including 93 ENROLL-HD participants (premanifest, n=22; early manifest n=47; advanced n=21, pediatric HD, n=3) and 17 healthy cohabitants. Fecal sample collection and DNA extraction were followed by shotgun sequencing with Illumina for taxonomic and functional profiling using the software GAIA. Alpha and beta diversity metrics, along with differential abundance analysis (DAA), were employed to investigate microbial differences across disease states. The DAA was conducted considering gender, Body Mass Index (BMI), and CAGExp as covariates. Redouts contributed to create a Dysbiosis Index (DI). <h3>Results/Outcome</h3> About 570 million reads allowed the identification of 3096 species across the entire cohort of samples. Alpha diversity did not change among cohorts. Beta diversity indicated an association between HD phase and microbial community structure, supporting the existence of distinct data clustering (PERMANOVA, p=0.03). DAA showed a difference in the distribution of species with a significant variability of 49 species in premanifest, 48 in early manifest, and 91 in advanced HD cohorts vs controls (adjusted p&lt;0.05). DI indicated significant differences in microbial community composition between the advanced and early manifest groups compared to controls, while there was some overlap between control and premanifest subjects. <h3>Conclusions</h3> Our shotgun approach revealed a substantial difference in the distribution, abundance and DI between HD and control populations.