Data_Sheet_6_Gut Microbial Profile Is Associated With the Severity of Social Impairment and IQ Performance in Children With Autism Spectrum Disorder.PDF

Background and Objective: Autism spectrum disorder (ASD) refers to a heterogeneous set of neurodevelopmental disorders with diverse symptom severity and comorbidities. Although alterations in gut microbiota have been reported in individuals with ASD, it remains unclear whether certain microbial pattern is linked to specific symptom or comorbidity in ASD. We aimed to investigate the associations between gut microbiota and the severity of social impairment and cognitive functioning in children with ASD.
Methods: A total of 261 age-matched children, including 138 children diagnosed with ASD, 63 with developmental delay or intellectual disability (DD/ID), and 60 typically developing (TD) children, were enrolled from the Shanghai Xinhua Registry. The children with ASD were further classified into two subgroups: 76 children diagnosed with ASD and developmental disorder (ASD+DD) and 62 with ASD only (ASD-only). The gut microbiome of all children was profiled and evaluated by 16S ribosomal RNA sequencing.
Results: The gut microbial analyses demonstrated an altered microbial community structure in children with ASD. The alpha diversity indices of the ASD+DD and ASD-only subgroups were significantly lower than the DD/ID or TD groups. At the genus level, we observed a decrease in the relative abundance of Prevotella. Simultaneously, Bacteroides and Faecalibacterium were significantly increased in ASD compared with DD/ID and TD participants. There was a clear correlation between alpha diversity and the Childhood Autism Rating Scale (CARS) total score for all participants, and this correlation was independent of IQ performance. Similar correlations with the CARS total score were observed for genera Bacteroides, Faecalibacterium, and Oscillospira. However, there was no single genus significantly associated with IQ in all participants.
Conclusions: Specific alterations in bacterial taxonomic composition and associations with the severity of social impairment and IQ performance were observed in children with ASD or ASD subgroups, when compared with DD/ID or TD groups. These results illustrate that gut microbiota may serve as a promising biomarker for ASD symptoms. Nevertheless, further investigations are warranted.

背景与目的：自闭症谱系障碍（Autism Spectrum Disorder, ASD）是一组异质性神经发育障碍，其症状严重程度与共病情况均存在显著差异。尽管已有研究报道自闭症患者存在肠道菌群（gut microbiota）失调，但目前仍不清楚是否存在特定的微生物模式与自闭症患者的特定症状或共病相关。本研究旨在探讨自闭症儿童肠道菌群与社会交往损害严重程度及认知功能之间的关联。
方法：本研究从上海新华登记队列（Shanghai Xinhua Registry）中纳入261名年龄匹配的儿童，其中138名确诊为自闭症谱系障碍，63名患有发育迟缓或智力障碍（developmental delay or intellectual disability, DD/ID），60名发育正常（typically developing, TD）。其中自闭症谱系障碍儿童进一步分为两个亚组：76名同时合并发育障碍的自闭症患儿（ASD+DD）以及62名单纯自闭症患儿（ASD-only）。所有受试者的肠道菌群均通过16S核糖体RNA（16S ribosomal RNA）测序进行分析与评估。
结果：肠道菌群分析显示，自闭症儿童的微生物群落结构发生了显著改变。ASD+DD亚组与ASD-only亚组的α多样性指数均显著低于DD/ID组与TD组。在属水平上，我们观察到普雷沃氏菌属（Prevotella）的相对丰度降低；同时，与DD/ID组及TD组相比，自闭症患儿的拟杆菌属（Bacteroides）和粪杆菌属（Faecalibacterium）相对丰度显著升高。所有受试者的α多样性指数与儿童自闭症评定量表（Childhood Autism Rating Scale, CARS）总分均存在显著相关性，且该相关性不受智商（IQ）表现的影响。拟杆菌属、粪杆菌属以及颤螺菌属（Oscillospira）的相对丰度同样与CARS总分存在类似相关性。然而，并未发现单一菌属与所有受试者的智商水平存在显著关联。
结论：与DD/ID组及TD组相比，自闭症儿童及其亚组的细菌分类组成存在特异性改变，且与社会交往损害严重程度及智商表现存在关联。上述结果表明，肠道菌群有望成为自闭症症状的潜在生物标志物（biomarker），但仍需开展进一步的研究加以验证。