Objective To observe the effects of acupuncture on spatial learning and memory ability,gut flora composition,intracerebral lipopolysaccharide content,and blood-brain barrier permeability in APP/PS1 mice.To explore the intrinsic mechanism of acupuncture in the treatment of Alzheimer′s disease.Methods 24 APP/PS1 mice were randomly divided into the model group,acupuncture group,and probiotic group,and 8 C57BL/6 mice of the same background were used as the normal control group.In the acupuncture group,acupuncture points were taken from"Baihui","YinTang",and"Zusanli"for 20 min.In the probiotic group,probiotics were given by gavage.The model group and normal control group received only restraint.The above interventions were performed once a day for 45 days.After 45 days of intervention,the feces of mice in each group were taken for 16s RNA,and spatial learning and memory skills in each group were observed by the Morris water maze test.The Lipopolysaccharide(LPS)in the brain was detected by immunofluorescence.The blood-brain barrier(BBB)structure was observed by transmission electron microscopy.Results Compared to the model group,Acupuncture improved the spatial learning and memory ability of APP/PS1 mice(P<0.05).It regulated species diversity and composition of APP/PS1 mice,and LPS was significantly decreased(P<0.05).Conclusion Acupuncture significantly improved spatial learning and memory in APP/PS1 mice,modulated BBB tight junction structure,and reduced hippocampal neuronal degeneration,and the effects were consistent with probiotics.The intrinsic mechanism of action is probably achieved by regulating intestinal flora and reducing LPS load.