Rhubarb ameliorates cognitive dysfunction in a rat model of Alzheimer’s disease through regulation of the intestinal microbiome

Objective:To determine the mechanism whereby rhubarb(Rheum tanguticum MAXIM.Ex BALF.)may ameliorate cognitive dysfunction through regulation of the intestinal microbiome.Methods:We used a rat model of human microbiome-associated(HMA)-AD to characterize the therapeutic effect of rhubarb on cognitive dysfunction by assessing learning and spatial memory,tissue pathology,and neurotransmitter expression in brain tissue.Then,16S rRNA gene sequencing was used to analyze the intestinal microbial composition of the rats before and after rhubarb intervention,to determine whether changes in the intestinal microbiome might underpin the beneficial effect of rhubarb on cognitive dysfunction.Results:Morris water maze experiments showed that the learning and spatial memory of HMAAD rats were improved after rhubarb administration.Examination of brain sections showed that rhubarb had a protective effect on neurons in the brain tissue of HMA-AD rats.Brain tissue neurotransmitter analysis showed that rhubarb significantly reduces the 5-hydorxytryptamine concentration in the hippocampus of HMA-AD rats(P Z.0013).Furthermore,rhubarb affected the abundance of the Lachnospiraceae_NK4A136_group and Lactobacillus in the large intestine.Conclusion:This study suggests that rhubarb ameliorates cognitive dysfunction in rats with HMA-AD by regulating the abundance of beneficial bacteria,which likely affects the concentration of 5-hydorxytryptamine in the hippocampus.