Effects of Oligosaccharides From Morinda officinalis on Gut Microbiota and Metabolome of APP/PS1 Transgenic Mice

Frontiers in Neurology

Lai Guoxiao¹  Zhao Jun²  Liang Hualun⁴  Chen Diling⁵  Zheng Chaoqun⁵  Tang Xiaocui⁵  Yang Jian⁵  Shuai Ou⁵  Xie Yizhen⁵  Yang Xin⁶  Hu Guoyan⁶  Liu Ting⁶ 

[1] College of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, China;Department of Obstetrics, Guangdong Women and Children Hospital, Guangzhou, China;Department of Pharmacy, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;Department of Pharmacy, The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China;State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, China;The Fifth Clinical School of Guangzhou Medical University, Guangzhou, China;

关键词: oligosaccharides of Morinda officinalis;    Alzheimer's disease;    gut microbiota;    metabolomics;    APP/PS1 transgenic mice;    metabolites;   

DOI  :  10.3389/fneur.2018.00412

来源: DOAJ

【 摘 要 】

Alzheimer's disease (AD), a progressive neurodegenerative disorder, lacks preclinical diagnostic biomarkers and therapeutic drugs. Thus, earlier intervention in AD is a top priority. Studies have shown that the gut microbiota influences central nervous system disorders and that prebiotics can improve the cognition of hosts with AD, but these effects are not well understood. Preliminary research has shown that oligosaccharides from Morinda officinalis (OMO) are a useful prebiotic and cause substantial memory improvements in animal models of AD; however, the mechanism is still unclear. Therefore, this study was conducted to investigate whether OMO are clinically effective in alleviating AD by improving gut microbiota. OMO were administered to APP/PS1 transgenic mice, and potential clinical biomarkers of AD were identified with metabolomics and bioinformatics. Behavioral experiments demonstrated that OMO significantly ameliorated the memory of the AD animal model. Histological changes indicated that OMO ameliorated brain tissue swelling and neuronal apoptosis and downregulated the expression of the intracellular AD marker Aβ1−42. 16S rRNA sequencing analyses indicated that OMO maintained the diversity and stability of the microbial community. The data also indicated that OMO are an efficacious prebiotic in an animal model of AD, regulating the composition and metabolism of the gut microbiota. A serum metabolomics assay was performed using UHPLC-LTQ Orbitrap mass spectrometry to delineate the metabolic changes and potential early biomarkers in APP/PS1 transgenic mice. Multivariate statistical analysis showed that 14 metabolites were significantly upregulated, and 8 metabolites were downregulated in the model animals compared to the normal controls. Thus, key metabolites represent early indicators of the development of AD. Overall, we report a drug and signaling pathway with therapeutic potential, including proteins associated with cognitive deficits in normal mice or gene mutations that cause AD.

【 授权许可】

Unknown