Exogenous lipase administration alters gut microbiota composition and ameliorates Alzheimer’s disease-like pathology in APP/PS1 mice

Ariane Menden, Davane Hall, Coral Hahn-Townsend, Courtney A. Broedlow, Utsav Joshi, Andrew Pearson, Fiona Crawford, James E. Evans, Nichole Klatt, Stefan Crynen, Michael Mullan, Ghania Ait-Ghezala

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Article number4797
JournalScientific reports
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
We thank Lin Shi from the Chalmers University of Technology, Gothenburg, Sweden, who supported us for the rdCV-RF and subsequent multiOmics integration in R.

Funding Information:
This work was supported by the Roskamp Institute and by a Sponsored Research Agreement between The Roskamp Institute and Enzymedica, Inc.

Publisher Copyright:
© 2022, The Author(s).

Fingerprint

Dive into the research topics of 'Exogenous lipase administration alters gut microbiota composition and ameliorates Alzheimer’s disease-like pathology in APP/PS1 mice'. Together they form a unique fingerprint.

Cite this