肠道菌群情况与发声和多种运动联合抽动障碍患儿神经递质、神经功能及T细胞亚群的相关性分析

Correlation analysis of gut microbiota with neurotransmitters,neurological functions,and T cell subsets in children with tic disorders

目的探讨发声和多种运动联合抽动障碍(又称抽动症)患儿肠道菌群分布情况与其神经递质、神经功能及T细胞亚群的相关性。方法以2020年5月—2023年5月南京中医药大学附属南京市中西医结合医院收治的97例抽动症患儿作为研究对象,通过耶鲁抽动症整体严重度量表(YGTSS)将所有患儿分为轻度组23例、中度组42例和重度组32例。采集所有患儿粪便样本,采用16S rRNA测序技术和Qiime软件进行肠道菌群α多样性分析[Chao1指数、observed species(Sobs)指数、Shannon指数、Simpson指数];测定T淋巴细胞亚群(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))和神经递质[5-羟色胺(5-HT)、多巴胺(DA)、γ-氨基丁酸(GABA)、去甲肾上腺素(NE)]水平;评估两组儿童神经功能;采用Pearson相关性分析探讨患儿肠道菌群与神经递质、神经功能及T细胞亚群的关系。结果与轻度组相比,中度组和重度组的YGTSS评分的运动性抽动、发声性抽动、总分更高(P<0.05);轻度组、中度组和重度组患儿的Chao1、Sobs、Shannon和Simpson指数比较,经方差分析,差异均有统计学意义(P<0.05);与轻度组相比,中度组和重度组的α多样性更低(P<0.05);轻度组、中度组和重度组患儿的CD4^(+)、CD8^(+)和CD4^(+)/CD8^(+)比较,经方差分析,差异均有统计学意义(P<0.05);与轻度组相比,中度组和重度组的CD4^(+)和CD4^(+)/CD8^(+)更低,CD8^(+)更高(P<0.05);与轻度组相比,中度组和重度组的5-HT和DA更高,GABA、NE、神经功能评分更低(P<0.05)。根据Pearson相关性分析结果,患儿Chao1、Sobs、Shannon和Simpson指数与5-HT、DA呈负相关(P<0.05),与CD4^(+)、GABA、NE和神经功能评分呈正相关(P<0.05)。结论肠道菌群与抽动症患儿的神经递质、神经功能和T细胞亚群密切相关。

Objective To explore the correlation between the distribution of gut microbiota and neurotransmitters,neurological functions,and T cell subsets in children with tic disorders.Methods A total of 97 children with tic disorders treated in our hospital from May 2020 to May 2023 were selected as research subjects.They were divided into mild(n=23),moderate(n=42),and severe(n=32)groups based on the Yale Global Tic Severity Scale(YGTSS).Fecal samples from all children were collected,and theα-diversity of gut microbiota[including Chao1 index,observed species richness(Sobs),Shannon index,and Simpson index]was analyzed using the 16S rRNA sequencing technology and the Qiime software.T lymphocyte subsets(CD4^(+),CD8^(+),CD4^(+)/CD8^(+))and neurotransmitters[5-hydroxytryptamine(5-HT),dopamine(DA),gamma-aminobutyric acid(GABA),and norepinephrine(NE)]were measured.Neurological functions of the two groups of children were assessed.The relationship between gut microbiota and neurotransmitters,neurological functions,and T cell subsets in the children was explored through Pearson correlation analysis.Results Compared to the mild group,the moderate and severe groups had higher motor and vocal tic scores as well as higher total scores as tested via YGTSS(P<0.05).When comparing the Chao1,Sobs,Shannon,and Simpson indices of children in the mild,moderate,and severe groups,significant statistical differences were found through ANOVA(P<0.05).Compared with the mild group,theα-diversity in the moderate and severe groups was lower(P<0.05).Comparisons of the counts of CD4^(+)and CD8^(+)T cells and ratios of CD4^(+)/CD8^(+)T cells among mild,moderate,and severe groups also showed statistically significant differences via variance analysis(P<0.05).Compared with the mild group,the moderate and severe groups had a lower count of CD4^(+)T cells and a lower ratio of CD4^(+)/CD8^(+)T cells,but a higher count of CD8^(+)T cells(P<0.05).Compared with the mild group,the moderate and severe groups had higher levels of 5-HT and DA,and lower levels of GABA,NE,and neurological function scores(P<0.05).According to Pearson correlation analysis,the Chao1,Sobs,Shannon,and Simpson indices were all negatively correlated with the levels of 5-HT and DA(P<0.05),and positively correlated with the count of CD4^(+)T cells,levels of GABA and NE,and neurological function scores(P<0.05).Conclusions The gut microbiota are closely related to neurotransmitters,neurological functions,and T cell subsets in children with tic disorders.