Abstract

Alzheimer’s disease (AD) represents the most common form of dementia in the elderly with no available disease modifying treatments. Altered gut microbial composition has been widely acknowledged as a common feature of AD, which potentially contributes to progression or onset of AD. To assess the hypothesis that Candida rugosa lipase (CRL), which has been shown to enhance gut microbiome and metabolite composition, can rebalance the gut microbiome composition and reduce AD pathology, the treatment effects in APPswe/PS1de9 (APP/PS1) mice were investigated. The analysis revealed an increased abundance of Acetatifactor and Clostridiales vadin BB60 genera in the gut; increased lipid hydrolysis in the gut lumen, normalization of peripheral unsaturated fatty acids, and reduction of neuroinflammation and memory deficits post treatment. Finally, we demonstrated that the evoked benefits on memory could be transferred via fecal matter transplant (FMT) into antibiotic-induced microbiome-depleted (AIMD) wildtype mice, ameliorating their memory deficits. The findings herein contributed to improve our understanding of the role of the gut microbiome in AD’s complex networks and suggested that targeted modification of the gut could contribute to amelioration of AD neuropathology.

Details

Title
Exogenous lipase administration alters gut microbiota composition and ameliorates Alzheimer’s disease-like pathology in APP/PS1 mice
Author
Menden Ariane 1 ; Hall Davane 2 ; Hahn-Townsend, Coral 2 ; Broedlow, Courtney A 3 ; Joshi Utsav 2 ; Pearson, Andrew 1 ; Crawford, Fiona 4 ; Evans, James E 2 ; Klatt Nichole 3 ; Crynen Stefan 1 ; Mullan, Michael 1 ; Ait-Ghezala Ghania 1 

 Roskamp Institute, Sarasota, USA (GRID:grid.417518.e) (ISNI:0000 0004 0430 2305); Open University, Milton-Keynes, UK (GRID:grid.10837.3d) (ISNI:0000 0000 9606 9301) 
 Roskamp Institute, Sarasota, USA (GRID:grid.417518.e) (ISNI:0000 0004 0430 2305) 
 University of Minnesota, Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657) 
 Roskamp Institute, Sarasota, USA (GRID:grid.417518.e) (ISNI:0000 0004 0430 2305); Open University, Milton-Keynes, UK (GRID:grid.10837.3d) (ISNI:0000 0000 9606 9301); James A. Haley Veterans’ Hospital, Tampa, USA (GRID:grid.281075.9) (ISNI:0000 0001 0624 9286) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2641596470
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.