Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
Department of Child Psychiatry, Shimada Ryoiku Medical Center for Challenged Children, Tokyo, Japan.
J Child Psychol Psychiatry. 2024 Sep;65(9):1184-1195. doi: 10.1111/jcpp.13962. Epub 2024 Apr 2.
Previous research has shown a significant link between gut microbiota in children with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). However, much remains unknown because of the heterogeneity of disorders and the potential confounders such as dietary patterns and control group variations.
Children aged 6-12 years who had been clinically diagnosed with ASD and/or ADHD, their unaffected neurotypical siblings, and non-related neurotypical volunteers were recruited cross-sectionally. The ASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule-2 (ADOS-2) in all patients, including those with ADHD. Standardized DNA extraction and sequencing methods were used to compare gut microbial alpha-diversity among the groups. Dietary diversity was calculated from a standardized dietary questionnaire form. We compared the difference in gut microbiome between patients with ASD and/or ADHD with neurotypical siblings and non-related neurotypical controls.
Ninety-eight subjects were included in the study (18 with ASD, 19 with ADHD, 20 with both ASD and ADHD, 13 neurotypical siblings, and 28 non-related neurotypical controls). The alpha-diversity indices, such as Chao 1 and Shannon index, showed a significant difference between the groups in a Linear mixed-effect model (F(4, 93) = 4.539, p = .02), (F(4, 93) = 3.185, p = .017), respectively. In a post-hoc pairwise comparison, patients with ASD had lower alpha-diversity compared with non-related controls after Bonferroni correction. Dietary diversity shown in Shannon index did not differ among the groups (F(4, 84) = 1.494, p = .211).
Our study indicates disorder-specific microbiome differences in patients with ASD. In future research on gut microbiota in neurodevelopmental disorders, it is necessary to consider the impact of ASD and ADHD co-occurrence, and strictly control for background information such as diet, to elucidate the gut-microbiota interaction in ASD and ADHD for exploring the potential of therapeutic interventions.
先前的研究表明，自闭症谱系障碍（ASD）和注意缺陷多动障碍（ADHD）儿童的肠道微生物群之间存在显著关联。然而，由于疾病的异质性以及饮食模式和对照组变化等潜在混杂因素，仍有许多未知因素。
本研究采用横断面研究的方法，招募了年龄在 6-12 岁之间的已被临床诊断为 ASD 和/或 ADHD 的儿童、其未受影响的神经典型兄弟姐妹以及非相关的神经典型志愿者。所有患者（包括患有 ADHD 的患者）均使用自闭症诊断观察量表-2（ADOS-2）进行 ASD 诊断确认。使用标准化的 DNA 提取和测序方法比较各组之间的肠道微生物α多样性。从标准化饮食问卷表中计算饮食多样性。我们比较了 ASD 和/或 ADHD 患者与神经典型兄弟姐妹和非相关神经典型对照组之间的肠道微生物组差异。
本研究共纳入 98 名受试者（18 名 ASD 患者、19 名 ADHD 患者、20 名 ASD 和 ADHD 共病患者、13 名神经典型兄弟姐妹和 28 名非相关神经典型对照）。线性混合效应模型显示，Chao1 和 Shannon 指数等α多样性指数在组间存在显著差异（F(4,93)=4.539, p=0.02），（F(4,93)=3.185, p=0.017）。在事后两两比较中，经过 Bonferroni 校正后，ASD 患者的α多样性低于非相关对照组。Shannon 指数显示的饮食多样性在各组之间没有差异（F(4,84)=1.494, p=0.211）。
本研究表明 ASD 患者存在特定于疾病的微生物组差异。在未来的神经发育障碍肠道微生物组研究中，有必要考虑 ASD 和 ADHD 共病的影响，并严格控制饮食等背景信息，以阐明 ASD 和 ADHD 中的肠道-微生物群相互作用，探索治疗干预的潜力。
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