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

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.