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

• Published in: Scientific reports 2022-03, Vol.12 (1), p.4797-17, Article 4797
• Main Authors: Menden, Ariane, Hall, Davane, Hahn-Townsend, Coral, Broedlow, Courtney A., Joshi, Utsav, Pearson, Andrew, Crawford, Fiona, Evans, James E., Klatt, Nichole, Crynen, Stefan, Mullan, Michael, Ait-Ghezala, Ghania
• Format: Article
• Language: English
• Subjects: 631/154/53/2421; 631/326/2565/2134; 631/378/1689/1283; 692/308/575; 692/4017; 692/53; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; Clostridiales - metabolism; Dementia disorders; Disease Models, Animal; Fatty acids; Gastrointestinal Microbiome - physiology; Humanities and Social Sciences; Inflammation; Intestinal microflora; Lipase; Memory; Memory Disorders; Metabolites; Mice; Mice, Transgenic; Microbiomes; Microbiota; multidisciplinary; Neurodegenerative diseases; Pathology; Presenilin 1; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-08840-7

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.