基于肠道菌群-代谢组学探讨归脾汤治疗心脾两虚型孤独症谱系障碍的作用及机制OA
Efficacy and mechanism of Guipi Decoction in the treatment of children with autism spectrum disorder of heart-spleen deficiency type based on microbiome-metabolomics
目的 观察归脾汤治疗心脾两虚型孤独症谱系障碍(ASD)患儿的疗效及对肠道菌群、血浆代谢物的影响.方法 选择2023 年9 月—2024 年6 月在湖南中医药大学第一附属医院儿童康复中心诊治及0~6 岁ASD 减免筛查符合入组标准的心脾两虚型ASD 患儿62 例,随机分为观察组和对照组,每组31 例.对照组给予康复训练干预,观察组给予康复训练干预及归脾汤口服,2组均治疗12 周.比较2 组治疗前后儿童孤独症评定量表(CARS)评分、孤独症儿童心理教育量表第3 版(PEP-3)评分、脾胃疾病症状量表评分及治疗后临床疗效;2 组末次治疗结束当天进行16S rDNA 肠道菌群测序和血浆代谢组学检测,并分析肠道菌群与血浆代谢组学的相关性.结果 2 组各30 例完成研究.与治疗前比较,治疗后2 组 CARS 评分和观察组脾胃疾病症状量表评分均明显降低(P 均<0.05),2 组 PEP-3 中各部分评分均明显升高(P 均<0.05);与对照组比较,治疗后观察组 CARS 评分和脾胃疾病症状量表评分均更低(P 均<0.05),PEP-3 中各部分评分均更高(P均<0.05).治疗后观察组总有效率明显高于对照组[93.3%(28/30)比 66.7%(20/30),P<0.05].肠道菌群测序显示,观察组中放线菌门(Actinobacteriota)及杜氏乳杆菌属(Dubosiella)、优杆菌属(Eubacterium)、双歧杆菌属(Bifidobacterium)相对丰度均明显高于对照组(P 均<0.05),普雷沃菌属(Prevotellaceae)相对丰度明显低于对照组(P<0.05);代谢组学分析共筛选出8 个显著差异代谢物,差异代谢物主要与氨基酸代谢、胆碱代谢、儿茶酚胺合成、鞘脂代谢等通路相关.Spearman 分析显示,L-谷氨酰胺(L-glutamine)水平与普雷沃菌属(Prevotellaceae)呈负相关,L-精氨酸(L-arginine)水平与普雷沃菌属(Prevotellaceae)呈正相关,L-酪氨酸(L-tyrosine)水平与单球菌属(Monoglobus)呈负相关.结论 归脾汤能明显改善 ASD 患儿的核心症状,可调控肠道微生物如杜氏乳杆菌等菌属丰度,影响与氨基酸代谢、胆碱代谢、儿茶酚胺合成、鞘脂代谢等通路相关的血浆代谢物水平.
Objective It is to observe the clinical efficacy of Guipi Decoction in the treatment of children with autism spectrum disorder(ASD)and its effects on gut microbiota and plasma metabolites.Methods Sixty-two children with ASD of heart-spleen deficiency type who met the inclusion criteria and underwent treatment at the Children's Rehabilitation Cen-ter of the First Affiliated Hospital of Hunan University of Chinese Medicine from September 2023 to June 2024,as well as those who received free ASD screening for children aged 0-6 years were selected and randomly assigned to an observation group and a control group,with 31 cases in each group.The control group was treated with rehabilitation training,while the observation group was treated with both rehabilitation training and Guipi Decoction via oral administration,both groups were treated for 12 weeks.The scores of Childhood Autism Rating Scale(CARS),Psychological Education Profile-3rd Edition(PEP-3),and Spleen-Stomach Disease Symptom Scale before and after treatment,as well as clinical efficacy after treat-ment were observed and compared between the two groups.On the day of the final treatment,16S rDNA gut microbiota se-quencing and plasma metabolomics testing were performed in the children of the two groups,and the correlation between gut microbiota and plasma metabolomics was analyzed.Results A total of 30 children in each group completed the study.The CARS scores of both groups and the Spleen-Stomach Disease Symptom Scale scores of the observation group were signifi-cantly decreased,while the scores of each part in PEP-3 of both groups were significantly increased after treatment com-pared with those before treatment(all P<0.05);the CARS scores and Spleen-Stomach Disease Symptom Scale scores of the observation group were significantly lower,while the scores of each part in PEP-3 were significantly higher than those of the control group after treatment(all P<0.05).After treatment,the overall response rate in the observation group was sig-nificantly higher than that in the control group[93.3%(28/30)vs 66.7%(20/30),P<0.05].Gut microbiota sequen-cing revealed that the relative abundances of the phylum Actinobacteriota,as well as the genera Dubosiella,Eubacterium,and Bifidobacterium in the observation group were all significantly higher than those in the control group(all P<0.05),while the relative abundance of the genus Prevotellaceae was significantly lower than that in the control group(P<0.05).Metabolomics analysis identified a total of 8 significantly differential metabolites,which were associated with pathways such as amino acid metabolism,choline metabolism,catecholamine synthesis and sphingolipid metabolism.Spearman's correla-tion analysis showed that the level of L-glutamine was negatively correlated with Prevotellaceae,the level of L-arginine was positively correlated with Prevotellaceae,and the level of L-tyrosine was negatively correlated with Monoglobus.Conclusion Guipi Decoction can significantly improve core symptoms in children with ASD,it can regulate the abundance of gut micro-biota such as Dubosiella,and influences the levels of plasma metabolites associated with pathways such as amino acid me-tabolism,choline metabolism,catecholamine synthesis and sphingolipid metabolism.
邹婷;张艺佳;吴喆;阳雅安;朱沁泉;谢映
湖南中医药大学第一附属医院,湖南 长沙 410007湖南中医药大学,湖南 长沙 410208湖南中医药大学第一附属医院,湖南 长沙 410007湖南中医药大学,湖南 长沙 410208湖南中医药大学第一附属医院,湖南 长沙 410007湖南中医药大学第一附属医院,湖南 长沙 410007
医药卫生
归脾汤孤独症谱系障碍肠道微生物代谢组学心脾两虚型
Guipi Decoctionautism spectrum disordergut microbiotametabolomicsheart-spleen deficiency syn-drome
《现代中西医结合杂志》 2026 (16)
2191-2198,2204,9
湖南省自然科学基金项目(2025JJ80933)湖南省卫生健康委2023年度卫生科研课题(D202306048765)湖南省中医药科研课题(B2023121,B20260024)
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