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Prebiotics modulate the microbiota-gut-brain axis and ameliorate cognitive impairment in APP/PS1 mice

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机构: [1]Department of Rehabilitation Medicine, Xuan Wu Hospital, Capital Medical University, 45 Chang Chun Street, Beijing 100053, China [2]Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China [3]Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China [4]Department of Rheumatology, the First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang 050031, Hebei, China [5]State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China [6]Department of Cardiovasology, the First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang 050031, Hebei, China [7]Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China [8]Department of Neurology, Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, China
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关键词: Alzheimer’s disease Microbiota–gut–brain axis Fructo-oligosaccharides Galacto-oligosaccharides Neuroinflammation

摘要:
Prebiotics, including fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), stimulate beneficial gut bacteria and may be helpful for patients with Alzheimer's disease (AD). This study aimed to compare the effects of FOS and GOS, alone or in combination, on AD mice and to identify their underlying mechanisms.Six-month-old APP/PS1 mice and wild-type mice were orally administered FOS, GOS, FOS + GOS or water by gavage for 6 weeks and then subjected to relative assays, including behavioral tests, biochemical assays and 16S rRNA sequencing.Through behavioral tests, we found that GOS had the best effect on reversing cognitive impairment in APP/PS1 mice, followed by FOS + GOS, while FOS had no effect. Through biochemical techniques, we found that GOS and FOS + GOS had effects on multiple targets, including diminishing Aβ burden and proinflammatory IL-1β and IL-6 levels, and changing the concentrations of neurotransmitters GABA and 5-HT in the brain. In contrast, FOS had only a slight anti-inflammatory effect. Moreover, through 16S rRNA sequencing, we found that prebiotics changed composition of gut microbiota. Notably, GOS increased relative abundance of Lactobacillus, FOS increased that of Bifidobacterium, and FOS + GOS increased that of both. Furthermore, prebiotics downregulated the expression levels of proteins of the TLR4-Myd88-NF-κB pathway in the colons and cortexes, suggesting the involvement of gut-brain mechanism in alleviating neuroinflammation.Among the three prebiotics, GOS was the optimal one to alleviate cognitive impairment in APP/PS1 mice and the mechanism was attributed to its multi-target role in alleviating Aβ pathology and neuroinflammation, changing neurotransmitter concentrations, and modulating gut microbiota.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.

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出版当年[2022]版:
大类 | 2 区 医学
小类 | 2 区 营养学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 营养学
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出版当年[2021]版:
Q2 NUTRITION & DIETETICS
最新[2023]版:
Q2 NUTRITION & DIETETICS

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [1]Department of Rehabilitation Medicine, Xuan Wu Hospital, Capital Medical University, 45 Chang Chun Street, Beijing 100053, China [2]Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China [3]Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China
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通讯机构: [2]Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China [3]Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing 100029, China
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