Mechanism of action of electroacupuncture targeting both brain and intestine on autistic rats based on intestinal flora and metabolomics
Objective To observe the effects of electroacupuncture(EA)targeting both brain and intestine on the social ability,intestinal flora,and metabolites in autistic rats.Methods The autistic rat model was prepared by intraperitoneal injection of sodium valproate,the successfully modeled rats were randomized into model group,basic EA group,acupuncture-medicine group,and EA targeting both brain and intestine group,with 10 rats in each group.In addition,10 normal rats were selected as control group.The basic EA group was given EA at"Baihui"(GV20),"Shenting"(GV24),and"Xinshu"(BL15)acupoints,the acupuncture-medicine group was treated with probiotics by gavage on the basis of the basic EA group,and the EA targeting both brain and intestine group was treated with EA at"Zusanli"(ST36)and"Quchi"(LI11)acupoints on the basis of the basic EA group,once a day,for 4 consecutive weeks.The behavioral changes were assessed by three-chamber social experiments,the intestinal flora distribution was analyzed by 16SrDNA sequencing,the differential metabolic components in plasma were analyzed by ultra-high performance liquid chromatography tandem mass spectrometry,and the correlation between intestinal flora and metabolomics was analyzed by Spearman.Results Compared with the control group,the social ability and social novelty of rats in the model group were weakened(P<0.01).Compared with the model group,the social novelty of the basic EA group,acupuncture-medicine group,and EA targeting both brain and intestine group was enhanced(P<0.01).Compared with the basic EA group,the social novelty of acupuncture-medicine group and the EA targeting both brain and intestine group was enhanced(P<0.01).The study of intestinal flora found that compared with the control group,the relative abundance of Campylobacter in the model group was up-regulated,while the relative abundance of Akkermansia muciniphila was down-regulated.Compared with the model group,the relative abundance of Campylobacter in the acupuncture-medicine group and the EA targeting both brain and intestine group was down-regulated,while the relative abundance of Akkermansia muciniphila was up-regulated.LEfSe analysis found that a total of 21 key bacteria were screened out in the EA targeting both brain and intestine group and the model group,such as compared with the model group,the EA targeting both brain and intestine group can up regulated Akkermansia muciniphila and Lactobacillus crispatus and down-regulated Clostridium.A total of 12 differential metabolites were screened out by metabolomics analysis,and pathway analysis showed that they were mainly related to amino acid metabolism,phosphate metabolism,purine metabolism,arachidonic acid metabolism,and other pathways.Conclusion EA at"Baihui"(GV20),"Shenting"(GV24),"Xinshu"(BL15),"Zusanli"(ST36),and"Quchi"(LI11)acupoints can significantly improve the social ability of autistic rats,regulate the abundance of intestinal flora such as Akkermansia muciniphila,and affect the level of metabolites at the same time.Moreover,there is a complex correlation between the changes of some metabolites and intestinal flora,which may be related to amino acid metabolism,phosphate metabolism,purine metabolism,arachidonic acid metabolism,and other pathways.
autism spectrum disorderelectroacupuncturetreatment targeting both brain and intestineintestinal florametabolomicssocial ability
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