Fecal microbiota transplantation alleviated Alzheimer\u2019s disease-like pathogenesis in APP/PS1 transgenic mice

Jing Sun,Tianyu Gong,Changwei Yang,Ziqing Song,Shiqing Ye,Dianhui Wei,Jiaming Liu,Danna Chen,Fangyan Wang,Yi Ling,Keyue Ye,Jingxuan Xu

doi:10.1038/s41398-019-0525-3

Abstract

Alzheimer’s disease (AD) is the most common dementia in the elderly. Treatment for AD is still a difficult task in clinic. AD is associated with abnormal gut microbiota. However, little is known about the role of fecal microbiota transplantation (FMT) in AD. Here, we evaluated the efficacy of FMT for the treatment of AD. We used an APPswe/PS1dE9 transgenic (Tg) mouse model. Cognitive deficits, brain deposits of amyloid-β (Aβ) and phosphorylation of tau, synaptic plasticity as well as neuroinflammation were assessed. Gut microbiota and its metabolites short-chain fatty acids (SCFAs) were analyzed by 16S rRNA sequencing and 1H nuclear magnetic resonance (NMR). Our results showed that FMT treatment could improve cognitive deficits and reduce the brain deposition of amyloid-β (Aβ) in APPswe/PS1dE9 transgenic (Tg) mice. These improvements were accompanied by decreased phosphorylation of tau protein and the levels of Aβ40 and Aβ42. We observed an increases in synaptic plasticity in the Tg mice, showing that postsynaptic density protein 95 (PSD-95) and synapsin I expression were increased after FMT. We also observed the decrease of COX-2 and CD11b levels in Tg mice after FMT. We also found that FMT treatment reversed the changes of gut microbiota and SCFAs. Thus, FMT may be a potential therapeutic strategy for AD.

Highlights

Alzheimer’s disease (AD) is the most common dementia in the elderly
The frequency and time spent in the target quadrant were much greater in the fecal microbiota transplantation (FMT) treatment group than in the Tg group (P < 0.05, Fig. 1c, d), indicating that FMT treatment was able to attenuate the impairment of spatial learning ability in Tg mice
This study demonstrated the neuroprotective effects of FMT against

Summary

Introduction

Alzheimer’s disease (AD) is the most common dementia in the elderly. The accumulation of amyloid-β (Aβ) and downstream pathological events (such as tau hyperphosphorylation, neuroinflammation, and synaptic loss) eventually lead to a gradual decline in cognitive function[1,2]. Recent evidence has demonstrated that AD is associated with abnormal gut microbiota[3,4]. The abundance of Helicobacteraceae and Desulfovibrionaceae at the family level and Odoribacter and Helicobacter at the specific bacteria from gut microbes produce metabolites, such as short-chain fatty acids (SCFAs), which can exert beneficial effects against neuropsychiatric disorders. The SCFA butyrate can alleviate cognition deficits[14] and enhance BDNF expression[15]. Our previous studies showed that butyrate could exert a protective effect against Parkinson’s disease[16], Sun et al Translational Psychiatry (2019)9:189

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Results

Conclusion