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Bidirectional interactions between curcumin and gut microbiota in transgenic mice with Alzheimer’s disease

  • Applied microbial and cell physiology
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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease with increasing prevalence worldwide, while there are no effective drugs at present. Curcumin, a natural polyphenolic substance isolated from turmeric, is a promising natural compound to combat AD, but its pharmacology remains to be fully understood for its poor in vivo bioavalibility. Inspired by the recently reported associations between gut microbiota and AD development, the present study investigated the interactions of curcumin with gut microbiota of APP/PS1 double transgenic mice from two directions: (i) curcumin influences gut microbiota, and (ii) gut microbiota biotransform curcumin. It was found that curcumin administration tended to improve the spatial learning and memory abilities and reduce the amyloid plaque burden in the hippocampus of APP/PS1 mice. On the one hand, curcumin administration altered significantly the relative abundances of bacterial taxa such as Bacteroidaceae, Prevotellaceae, Lactobacillaceae, and Rikenellaceae at family level, and Prevotella, Bacteroides, and Parabacteroides at genus level, several of which have been reported to be key bacterial species associated with AD development. On the other hand, a total of 8 metabolites of curcumin biotransformed by gut microbiota of AD mice through reduction, demethoxylation, demethylation and hydroxylation were identified by HPLC-Q-TOF/MS, and many of these metabolites have been reported to exhibit neuroprotective ability. The findings provided useful clues to understand the pharmacology of curcumin and microbiome-targeting therapies for AD.

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Funding

This work was supported by the Shandong Provincial Key Research and Development Program (Grant No. 2018GSF121001), Shandong Provincial Natural Science Foundation (Grant Nos. ZR2018MH010 and ZR2019MH020), University Youth Innovation Team of Shandong Province (Grant No. 2019KJK017), and Talent Program of Zibo.

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Author notes

  1. Zhen-Zhen Sun and Xin-Yu Li contributed equally to this work.

Authors and Affiliations

  1. Institute of Biomedical Research, Shandong University of Technology, Zibo, Shandong, People’s Republic of China

    Zhen-Zhen Sun, Xin-Yu Li, Sai Wang, Liang Shen & Hong-Fang Ji

  2. Zibo Key Laboratory of New Drug Development of Neurodegenerative diseases, Shandong Provincial Research Center for Bioinformatic Engineering and Technique, School of Life Sciences, Shandong University of Technology, Zibo, Shandong, People’s Republic of China

    Zhen-Zhen Sun, Xin-Yu Li, Sai Wang, Liang Shen & Hong-Fang Ji

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  1. Zhen-Zhen Sun
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  2. Xin-Yu Li
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  3. Sai Wang
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  4. Liang Shen
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  5. Hong-Fang Ji
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Contributions

HFJ and LS conceived and directed the study. ZZS, XYL, and SW performed the experiments. ZZS, XYL, LS, and HFJ analyzed the data, drafted and revised the manuscript.

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Correspondence to Liang Shen or Hong-Fang Ji.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Sun, ZZ., Li, XY., Wang, S. et al. Bidirectional interactions between curcumin and gut microbiota in transgenic mice with Alzheimer’s disease. Appl Microbiol Biotechnol 104, 3507–3515 (2020). https://doi.org/10.1007/s00253-020-10461-x

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  • DOI: https://doi.org/10.1007/s00253-020-10461-x

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