菖菊止动方对抽动障碍患儿肠道菌群的影响

Effect of Changju Zhidong Prescription on Intestinal Flora in Children with Tic Disorder

摘要:

目的 探讨菖菊止动方对抽动障碍（TD）患儿肠道菌群结构的调节作用。方法 选取2020年11月至2022年1月于至北京中医药大学东直门医院儿科门诊的24例TD患儿为观察组，8例健康儿童为作为正常组。观察组予菖菊止动方连续治疗12周，采用耶鲁综合抽动严重程度量表（YGTSS）、中医证候积分、儿童胃肠道中医症状评价量表积分观察临床疗效，同时收集正常组和观察组治疗前及治疗12周后的粪便样本，采用16S rDNA高通量测序技术探索菖菊止动方对患儿肠道菌群分布的影响。结果 与治疗前比较，观察组经过12周治疗后YGTSS、中医证候积分、儿童胃肠道中医症状评价量表积分明显降低（P<0.05）；alpha多样性中Simpson、Pielou-e指数明显降低（P<0.05）。治疗前，观察组的Streptococcus parasanguini相对丰度明显高于正常组，而柠檬酸杆菌属、乳酸杆菌属、乳酪杆菌属、未分类的蘑菇伞菌属、臭菌属等11个菌群的相对丰度则明显低于正常组。与治疗前比较，观察组经过12周治疗后未分类的瘤胃球菌种、瘤胃球菌属相对丰度明显降低，粪臭杆菌属（Olsenella）、Olsenella sp DNF00959、醋弧菌属（Acetivibrio）、uncultured Acetivibrio sp等6个菌群的相对丰度明显升高。功能富集分析显示，菖菊止动方调节肠道菌群的主要通路有细菌分泌系统、昆虫激素生物合成、柠檬烯和蒎烯降解、新生霉素的生物合成、哌啶和吡啶生物碱的生物合成。结论 TD患儿的发病伴随肠道菌群紊乱，菖菊止动方能够改善患儿的核心症状和胃肠症状，提高TD患儿的肠道有益菌、降低有害菌丰度，其可能通过萜类和聚酮类代谢发挥作用。

Abstract:

Objective To investigate the regulatory effect of Changju Zhidong prescription on gut microbiota structure of children with tic disorder（TD）.Method Twenty-four children with TD who visited the pediatric outpatient clinic of Dongzhimen Hospital of Bejjing University of Chinese Medicine from November 2020 to January 2022 were selected as the observation group， and eight healthy children were selected as the normal group. The observation group was treated with Changju Zhidong prescription for 12 weeks， and the clinical efficacy was observed by Yale global tic severity scale（YGTSS）， traditional Chinese medicine（TCM） syndrome score， and score of TCM symptom evaluation scale for pediatric gastrointestinal tract. Meanwhile， The fecal samples of the observation and normal groups were collected before and after treatment， and 16S rDNA sequencing was used to explore the effects of Changju Zhidong prescription on the distribution of gut microbiota of the children.Result Compared with the pre-treatment， the YGTSS， TCM syndrome score， and score of TCM symptom evaluation scale for pediatric gastrointestinal tract of the observation group were significantly reduced after 12 weeks of treatment（P<0.05）， Simpson and Pieloue indices in alpha diversity were significantly reduced（P<0.05）. Before treatment， the relative abundance of Streptococcus parasanguini in the observation group was significantly higher than that of the normal group， while the relative abundances of Citrobacter， Lactobacillus， Lacticaseibacillus， Muribaculaceae unclassified， Odoribacter and 7 other bacterial groups were significantly lower than that in the normal group. Compared with the pre-treatment， the observation group showed a significant decrease in Ruminococcus torques group unclassified and Ruminococcus torques group， and a significant increase in Olsenella， Acetivibrio and 4 other bacterial groups. Functional enrichment analysis showed that the main pathways of Changju Zhidong prescription regulating gut microbiota were bacterial secretion system， insect hormone biosynthesis， limonene and pinene degradation， novobiocin biosynthesis， tropane piperidine and pyridine alkaloid biosynthesis.Conclusion The pathogenesis of children with TD is accompanied by intestinal flora disorders， and Changju Zhidong prescription can improve core and gastrointestinal symptoms， increase the abundance of beneficial and decrease the abundance of harmful gut microbiota in children with TD， and its mechanism may be through the metabolism of terpenoids and polyketides.