National Health Commission (NHC) Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.
Department of Pediatrics, Shandong University Qilu Hospital, Jinan, Shandong, China.
Gut. 2022 Aug;71(8):1588-1599. doi: 10.1136/gutjnl-2021-325115. Epub 2021 Dec 20.
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, and , 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.
最近的研究提供了自闭症谱系障碍（ASD）肠道微生物组的见解；然而，由于在儿童单一阶段的采样有限，这些研究受到限制。在此，我们旨在揭示 ASD 大样本队列中肠道微生物组的发育特征，并结合影响肠道微生物组的个体间因素。
我们招募了 773 名 ASD 患者（年龄 16 个月至 19 岁）和 429 名神经典型（NT）发育患者（年龄 11 个月至 15 岁）的大样本队列，通过 16S rRNA 测序确定不同年龄肠道微生物组的动态变化。
在 ASD 患者中，我们观察到肠道微生物组的发展存在明显但渐进的偏差，其特征为持续降低的 alpha 多样性、早期不可持续的不成熟微生物群、20 个操作分类单元（OTUs）的丰度改变、分类检测率降低和 325 个受年龄依赖模式影响的微生物代谢功能失调。我们进一步揭示了 ASD 患者在 3 岁之前广泛改变的微生物关系，这些关系与 ASD 组的行为、睡眠和胃肠道症状严重程度相关。这项分析表明，由 2 个 OTUs（和）和 17 个微生物代谢功能组成的组合特征可以有效地在发现组（AUC=0.86）、验证 1 组（AUC=0.78）、验证 2 组（AUC=0.82）和验证 3 组（AUC=0.67）中区分 ASD 和 NT 患者。
我们的大样本队列结合临床症状分析，突出了肠道微生物组在 ASD 发病机制中的关键调节剂，并强调了在未来 ASD 的临床应用中监测和靶向肠道微生物组的重要性。
