Menozzi, Elisa;
Geiger, Mallia;
Meslier, Victoria;
Fierli, Federico;
Gilles, Marine;
Chau, Kai-Yin;
David, Aymeric;
... Schapira, Anthony HV; + view all
(2025)
Exploring the relationship between GBA1 host genotype and gut microbiome in the GBA1L444P/WT mouse model: implications for Parkinson’s disease pathogenesis.
Frontiers in Neuroscience
, 19
, Article 1546203. 10.3389/fnins.2025.1546203.
Preview |
Text
fnins-19-1546203.pdf - Published Version Download (1MB) | Preview |
Abstract
Background: Heterozygous variants in GBA1 are the commonest genetic risk factor for Parkinson’s 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: This study aimed to evaluate whether heterozygosity for the GBA1 pathogenic L444P variant can cause perturbations in gut microbiome composition. // Methods: Faecal samples collected from GBA1L444P/WT and GBA1WT/WT mice at 3 and 6 months of age were analysed through shotgun metagenomic sequencing. // Results: No differences in α- and β-diversities were detected between genotyped groups, at either time point. Overall, we found a little variation in the gut microbiome composition and functional potential between GBA1L444P/WT and GBA1WT/WT mice over time. // Conclusion: Host GBA1 genotype does not impact gut microbiome structure and composition in the presented GBA1L444P/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.
| Type: | Article |
|---|---|
| Title: | Exploring the relationship between GBA1 host genotype and gut microbiome in the GBA1L444P/WT mouse model: implications for Parkinson’s disease pathogenesis |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnins.2025.1546203 |
| Publisher version: | https://doi.org/10.3389/fnins.2025.1546203 |
| Language: | English |
| Additional information: | Copyright © 2025 Menozzi, Geiger, Meslier, Fierli, Gilles, Chau, David, Shahar Golan, Famechon, Koletsi, Morabito, Quinquis, Pons, Ehrlich, Macnaughtan, Almeida and Schapira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | Gut microbiome, microbiota-gut-brain axis, Parkinson disease, glucocerebrosidase, GBA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10215768 |
Archive Staff Only
 |
View Item |
