Deviated and early unsustainable stunted development of gut microbiota in children with autism spectrum disorder.
Deviated and early unsustainable stunted development of gut microbiota in children with autism spectrum disorder.
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自闭症谱系障碍儿童肠道菌群发育异常且早期不可持续
DOI：
10.1136/gutjnl-2021-325115
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发表时间：
2022-08
期刊：
影响因子：
24.5
通讯作者：
Wang, Yichao
中科院分区：
文献类型：
--
作者：
Lou, Mingxing;Cao, Aihua;Jin, Cuiyuan;Mi, Kai;Xiong, Xiyue;Zeng, Zhaoyang;Pan, Xu;Qie, Jinlong;Qiu, Shangfeng;Niu, Yaofang;Liang, Hao;Liu, Yanping;Chen, Lin;Liu, Zhi;Zhao, Qing;Qiu, Xiyan;Jin, Yuanxiang;Sheng, Xiaoqi;Hu, Zhibin;Jin, Gulei;Liu, Jingshi;Liu, Xingyin;Wang, Yichao
最近的研究为自闭症谱系障碍（ASD）的肠道微生物群提供了见解；然而，由于在儿童单一阶段的抽样有限，这些研究受到限制。在此，我们旨在揭示大量ASD患者肠道微生物群的发育特征，并结合影响肠道微生物群的个体间因素。采用16S rRNA测序技术，研究了773名ASD患者（年龄16个月至19岁）和429名神经正常（NT）发育患者（年龄11个月至15岁）在不同年龄阶段肠道微生物群的动态变化。在ASD受试者中，我们观察到肠道微生物群发育出现明显但渐进的偏差，其特征是α多样性持续下降，早期不可持续的未成熟微生物群，20个操作分类单位（otu）的丰度改变，分类单元检出率下降，325个微生物代谢功能不受调节，具有年龄依赖性模式。我们进一步揭示了微生物关系在3岁前的ASD中发生了广泛的变化，这与ASD组的行为、睡眠和胃肠道症状的严重程度有关。结果表明，在发现组（曲线下面积(AUC)=0.86）、验证组1 （AUC=0.78）、验证组2 （AUC=0.82）和验证组3 （AUC=0.67）中，2组otu、Veillonella和enterobacteraceae微生物代谢功能和17种微生物代谢功能的组合特征能够有效地区分ASD和NT受试者。我们的大队列研究结合临床症状分析，突出了肠道微生物群在ASD发病机制中的关键调节因子，并强调了肠道微生物群监测和靶向治疗在未来ASD临床应用中的重要性。
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. 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. 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. 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.
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影响因子：
64.8
作者：
Kim S;Kim H;Yim YS;Ha S;Atarashi K;Tan TG;Longman RS;Honda K;Littman DR;Choi GB;Huh JR
通讯作者：
Huh JR
影响因子：
11.1
作者：
Golubeva AV;Joyce SA;Moloney G;Burokas A;Sherwin E;Arboleya S;Flynn I;Khochanskiy D;Moya-Pérez A;Peterson V;Rea K;Murphy K;Makarova O;Buravkov S;Hyland NP;Stanton C;Clarke G;Gahan CGM;Dinan TG;Cryan JF
通讯作者：
Cryan JF
影响因子：
4.3
作者：
Mallick H;Rahnavard A;McIver LJ;Ma S;Zhang Y;Nguyen LH;Tickle TL;Weingart G;Ren B;Schwager EH;Chatterjee S;Thompson KN;Wilkinson JE;Subramanian A;Lu Y;Waldron L;Paulson JN;Franzosa EA;Bravo HC;Huttenhower C
通讯作者：
Huttenhower C
自闭症谱系障碍。
DOI：
10.1038/s41572-019-0138-4
发表时间：
2020-01-16
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Lord C;Brugha TS;Charman T;Cusack J;Dumas G;Frazier T;Jones EJH;Jones RM;Pickles A;State MW;Taylor JL;Veenstra-VanderWeele J
通讯作者：
Veenstra-VanderWeele J
影响因子：
5.8
作者：
Galkin, Fedor;Mamoshina, Polina;Zhavoronkov, Alex
通讯作者：
Zhavoronkov, Alex