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BRIEF RESEARCH REPORT article
Front. Neurosci.
Sec. Gut-Brain Axis
Volume 19 - 2025 |
doi: 10.3389/fnins.2025.1546203
This article is part of the Research Topic Exploring Gut Neuroimmunology: focus on the enteric nervous system in health and disease View all articles
Exploring the relationship between GBA1 host genotype and gut microbiome in the GBA1 L444P/WT mouse model: Implications for Parkinson disease pathogenesis
Provisionally accepted
Elisa Menozzi 1,2
Mallia Geiger 2,3* Victoria Meslier 2,3* Federico Fierli 1,2* Marine Gilles 3* Kai-Yin Chau 1,2* Aymeric David 2,3*
Revi Shahar Golan 1,2 Alexandre Famechon 2,3* Sofia Koletsi 1,2*
Christian Morabito 2,3 Benoit Quinquis 2,3* Nicolas Pons 2,3* Stanislav Dusko Ehrlich 1,2* Jane Macnaughtan 2,4* Mathieu Almeida 2,3* Anthony HV Schapira 1,2*- 1 Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, London, United Kingdom
- 2 Aligning Science Across Parkinson’s (ASAP), Chevy Chase, Maryland, United States
- 3 MetaGenoPoliS, Université Paris-Saclay, Jouy-en-Josas, Île-de-France, France
- 4 Institute for Liver and Digestive Health, University College London, London, England, United Kingdom
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.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.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.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.
Keywords: gut microbiome, Microbiota-gut-brain axis, Parkinson Disease, Glucocerebrosidase, GBA
Received: 16 Dec 2024; Accepted: 03 Feb 2025.
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). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor 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.
* Correspondence:
Mallia Geiger, Aligning Science Across Parkinson’s (ASAP), Chevy Chase, Maryland, United States
Victoria Meslier, Aligning Science Across Parkinson’s (ASAP), Chevy Chase, Maryland, United States
Federico Fierli, Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, London, United Kingdom
Marine Gilles, MetaGenoPoliS, Université Paris-Saclay, Jouy-en-Josas, 78350, Île-de-France, France
Kai-Yin Chau, Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, London, United Kingdom
Aymeric David, Aligning Science Across Parkinson’s (ASAP), Chevy Chase, Maryland, United States
Alexandre Famechon, Aligning Science Across Parkinson’s (ASAP), Chevy Chase, Maryland, United States
Sofia Koletsi, Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, London, United Kingdom
Benoit Quinquis, Aligning Science Across Parkinson’s (ASAP), Chevy Chase, Maryland, United States
Nicolas Pons, Aligning Science Across Parkinson’s (ASAP), Chevy Chase, Maryland, United States
Stanislav Dusko Ehrlich, Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, London, United Kingdom
Jane Macnaughtan, Aligning Science Across Parkinson’s (ASAP), Chevy Chase, Maryland, United States
Mathieu Almeida, Aligning Science Across Parkinson’s (ASAP), Chevy Chase, Maryland, United States
Anthony HV Schapira, Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, London, United Kingdom
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