Microbes have deserved broader attention as causal factors in Alzheimer’s disease (AD), a neurodegenerative disorder. The senescence-accelerated mouse prone 8 (SAMP8) strain, a spontaneous mice of accelerated aging, are considered a robust model for sporadic AD. LW-AFC, an herbal medicine, was prepared from LiuweiDihuang decoction, which is a classical traditional Chinese medicine prescription. Here, we showed that the treatment of LW-AFC improved cognitive impairments of SAMP8 mice, including spatial learning and memory ability, active avoidance response, and object recognition memory capability. Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units (OTUs) in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1 (SAMR1) strains, the control of SAMP8 mice. The treatment of LW-AFC altered 22 (16 increased and 6 decreased) OTUs in SAMP8 mice and among them, 15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice. We further showed that there were 7 (3 negative and 4 positive correlation) OTUs significantly correlated with all the three types of cognitive abilities, at the order level, including Bacteroidales, Clostridiales, Desulfovibrionales, CW040, and two unclassified orders. LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice. Our results indicate that the effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.
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