Effect of a Compound Chinese Herbal Medicine on Cognitive Dysfunction and Gut Microbiota in the Model Mouse with Alzheimer’s Disease

In this study, the model of transgenic mouse with Alzheimer’s disease (AD) was used to explore the potential mechanism of Compound Chinese Herbal Medicine (CCHM) based on Xiaoyaosan in alleviating the symptoms of AD. The effects of CCHM on cognitive dysfunction and fecal microbiota structure, composition and function in AD model mouse was investigated by using behavioral tests (including escaped latency and number of crossing the target platformin Morris water maze experiment) and 16S rRNA gene sequencing. Compared with AD group, the behavioral tests results showed that CCHM could improve the cognitive function of mouse, including shorten escaped latency and increased the number of crossing the platform (P<0.05). After CCHM treatment, the Alpha diversity of fecal microbiota increased, and the fecal bacterial profiles of the CCHM group deviated from those of the AD group, and the microbial communities of the CCHM group were close to those of the wild-type (WT) normal mouse. Furthermore, compared with WT group, the relative abundance of OTU345, OTU380 and OTU264 significantly decreased in AD group (P<0.05), while it was obviously enhanced after CCHM intervention (P<0.05), in which OTU345 and OTU380 belonged to Lachnospiraceae, a butyrate-producing bacterium. In addition, by analyzing the level of intestinal microflora in mice, it was also found that, compared with WT group, the relative abundance of Lachnospiraceae in AD group decreased significantly (P<0.05), while the relative abundance of Lachnospiraceae increased significantly after CCHM intervention (P<0.05).Finally, the 16S rRNA gene function prediction results showed that CCHM had a certain regulatory effect on gut microbial dysfunction in AD model mice. Therefore, CCHM could improve the symptoms of AD mice and affected their intestinal flora, providing a theoretical basis for the identification of its potential mechanism of action.