Microbiome alterations are associated with apolipoprotein E mutation in Octodon degus and humans with Alzheimer's disease

Guido Zampieri; Léa Cabrol; Claudio Urra; Eduardo Castro-Nallar; Guillaume Schwob; David Cleary; Claudio Angione; Robert M J Deacon; Michael J Hurley; Patricia Cogram

doi:10.1016/j.isci.2024.110348

Microbiome alterations are associated with apolipoprotein E mutation in Octodon degus and humans with Alzheimer's disease

iScience. 2024 Jun 22;27(8):110348. doi: 10.1016/j.isci.2024.110348. eCollection 2024 Aug 16.

Authors

Guido Zampieri¹, Léa Cabrol^{2

3

4}, Claudio Urra², Eduardo Castro-Nallar⁵, Guillaume Schwob⁴, David Cleary⁶, Claudio Angione¹, Robert M J Deacon², Michael J Hurley^{2

7}, Patricia Cogram^{2

8}

Affiliations

¹ School of Computing, Engineering and Digital Technologies, Department of Computer Science and Information Systems, Teesside University, Middlesbrough, Tees Valley TS1 3BX, UK.
² Institute of Ecology and Biodiversity, Department of Ecological Sciences, Faculty of Science, Universidad de Chile, Las Palmeras 3425, Santiago 7800003, Chile.
³ Aix Marseille University, University Toulon, CNRS, IRD, Méditerranéen Institute of Océanographie (MIO) UM 110, Avenue de Luminy, 13009 Marseille, France.
⁴ Millennium Institute Biodiversity of Antarctic and Subantarctic Ecosystems (BASE), Las Palmeras 3425, Santiago 7800003, Chile.
⁵ Center for Bioinformatics and Integrative Biology, Universidad Andres Bello, Avenida República 239, Santiago 7591538, Chile.
⁶ School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
⁷ Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
⁸ Department of Anatomy and Neurobiology, School of Medicine, B240 Med Sci, University of California, Irvine, Irvine, CA 92697, USA.

Abstract

Gut microbiome dysbiosis is linked to many neurological disorders including Alzheimer's disease (AD). A major risk factor for AD is polymorphism in the apolipoprotein E (APOE) gene, which affects gut microbiome composition. To explore the gut-brain axis in AD, long-lived animal models of naturally developing AD-like pathologies are needed. Octodon degus (degu) exhibit spontaneous AD-like symptoms and ApoE mutations, making them suitable for studying the interplay between AD genetic determinants and gut microbiome. We analyzed the association between APOE genotype and gut microbiome in 50 humans and 32 degu using16S rRNA gene amplicon sequencing. Significant associations were found between the degu ApoE mutation and gut microbial changes in degu, notably a depletion of Ruminococcaceae and Akkermansiaceae and an enrichment of Prevotellaceae, mirroring patterns seen in people with AD. The altered taxa were previously suggested to be involved in AD, validating the degu as an unconventional model for studying the AD/microbiome crosstalk.

Keywords: Biological sciences; Molecular neuroscience; Natural sciences; Neuroscience; Omics.