Exploring the relationship between GBA1 host genotype and gut microbiome in the GBA1L444P/WT mouse model: Implications for Parkinson disease pathogenesis
Output Details
Description
**Background** Heterozygous variants in *GBA1* are the commonest genetic risk factor for Parkinson disease (PD) but penetrance is incomplete. *GBA1* dysfunction can cause gastrointestinal disturbances and microbiome changes in preclinical models. Mounting evidence suggests that the microbiota-gut-brain axis is potentially implicated in PD pathogenesis. Whether the gut microbiome composition is influenced by host *GBA1* genetics in heterozygosis has never been explored.
**Objectives** To evaluate whether heterozygosity for the *GBA1* pathogenic L444P variant can cause perturbations in gut microbiome composition.
**Methods** Faecal samples collected from *GBA1*L444P/WT and *GBA1*WT/WT mice at 3 and 6 months of age were analysed through shotgun metagenomic sequencing.
**Results** No differences in α- and β-diversity were detected between genotyped groups, at either time points. Overall, we found a little variation of the gut microbiome composition and functional potential between *GBA1*L444P/WT and *GBA1*WT/WT mice over time.
**Conclusion** Host *GBA1* genotype does not impact gut microbiome structure and composition in the presented *GBA1*L444P/WT mouse model. Studies investigating the effect of a second hit on gut physiology and microbiome composition could explain the partial penetrance of *GBA1*variants in PD.
Identifier (DOI)
10.1101/2024.12.15.627490
