刘星吟+王益超+曹爱华等GUT:揭示自闭症大队列肠菌发育规律
创作:DMG-Quasimodo 审核:mildbreeze 01月01日
  • 纳入773名自闭症(ASD)和429名神经正常发育(NT)儿童,用16S测序分析不同年龄段的肠道菌群变化;
  • 与NT儿童相比,ASD患儿的肠道菌群发育逐渐偏离正常轨道:α多样性持续较低、早期菌群持续不稳定不成熟、常见菌属检出率较低(提示其定植有困难)、3岁前的细菌间关系明显改变、20个OTU丰度和325个菌群代谢功能改变,且变化模式具有年龄依赖性;
  • 多个OTU、菌群功能及细菌关系的变化,与行为、睡眠和胃肠症状严重程度相关;
  • 结合韦荣球菌属和肠杆菌科及17个细菌代谢功能建立诊断模型,可有效区分ASD和NT儿童。
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很多研究表明自闭症谱系障碍(ASD)与肠道菌群有密切关系,然而,这些研究存在样本量小以及采样年龄段单一的限制性。ASD儿童肠道菌群发育的动态特征及其与临床症状之间的关联仍待揭示。Gut最新发表了南京医科大学刘星吟、湖南省妇幼保健院王益超、山东大学齐鲁医院曹爱华等人的工作,报道了目前全球最大样本分析的自闭症儿童肠道菌群发育特征。该研究在我国的多地域大型队列中(包含1202名ASD儿童和对照儿童,及20名健康成人),从菌群的组成、多样性、成熟、菌群内的微生物关系、特定细菌类群和菌群代谢功能等层面,揭示了ASD患儿不同年龄阶段(从约1岁至青春期)的肠道菌群发展变化特征,以及个体间因素的影响,并建立了基于菌群的跨年龄/地域的ASD诊断模型,在3-6岁儿童中的表现尤其优异。这项工作突出了“年龄”这一因素在研究ASD肠道菌群中的重要性,为肠道菌群如何参与ASD发病机理提供了重要线索。
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Gut [IF:31.793]

Deviated and early unsustainable stunted development of gut microbiota in children with autism spectrum disorder

自闭症谱系障碍患儿肠道微生物群的偏离和早期不可持续的迟缓发育

10.1136/gutjnl-2021-325115

2021-12-20, Article

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Objective: Recent studies have provided insights into the gut microbiota in autism spectrum disorder (ASD); however, these studies were restricted owing to limited sampling at the unitary stage of childhood. Herein, we aimed to reveal developmental characteristics of gut microbiota in a large cohort of subjects with ASD combined with interindividual factors impacting gut microbiota.
Design: A large cohort of 773 subjects with ASD (aged 16 months to 19 years), 429 neurotypical (NT) development subjects (aged 11 months to 15 years) were emolyed to determine the dynamics change of gut microbiota across different ages using 16S rRNA sequencing.
Result: In subjects with ASD, we observed a distinct but progressive deviation in the development of gut microbiota characterised by persistently decreased alpha diversity, early unsustainable immature microbiota, altered aboudance of 20 operational taxonomic units (OTUs), decreased taxon detection rate and 325 deregulated microbial metabolic functions with age-dependent patterns. We further revealed microbial relationships that have changed extensively in ASD before 3 years of age, which were associated with the severity of behaviour, sleep and GI symptoms in the ASD group. This analysis demonstrated that a signature of the combination of 2 OTUs, Veillonella and Enterobacteriaceae, and 17 microbial metabolic functions efficiently discriminated ASD from NT subjects in both the discovery (area under the curve (AUC)=0.86), and validation 1 (AUC=0.78), 2 (AUC=0.82) and 3 (AUC=0.67) sets.
Conclusion: Our large cohort combined with clinical symptom analysis highlights the key regulator of gut microbiota in the pathogenesis of ASD and emphasises the importance of monitoring and targeting the gut microbiome in future clinical applications of ASD.

First Authors:
Mingxing Lou,Aihua Cao,Cuiyuan Jin,Kai Mi

Correspondence Authors:
Gulei Jin,Jingshi Liu,Xingyin Liu,Yichao Wang

All Authors:
Mingxing Lou,Aihua Cao,Cuiyuan Jin,Kai Mi,Xiyue Xiong,Zhaoyang Zeng,Xu Pan,Jinlong Qie,Shangfeng Qiu,Yaofang Niu,Hao Liang,Yanping Liu,Lin Chen,Zhi Liu,Qing Zhao,Xiyan Qiu,Yuanxiang Jin,Xiaoqi Sheng,Zhibin Hu,Gulei Jin,Jingshi Liu,Xingyin Liu,Yichao Wang

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