Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
Department of Biological Sciences, Wellesley College, 106 Central Street, Wellesley, MA, 02481, USA.
Mol Autism. 2024 May 17;15(1):21. doi: 10.1186/s13229-024-00597-2.
Identifying modifiable risk factors of autism spectrum disorders (ASDs) may inform interventions to reduce financial burden. The infant/toddler gut microbiome is one such feature that has been associated with social behaviors, but results vary between cohorts. We aimed to identify consistent overall and sex-specific associations between the early-life gut microbiome and autism-related behaviors.
Utilizing the Environmental influences on Children Health Outcomes (ECHO) consortium of United States (U.S.) pediatric cohorts, we gathered data on 304 participants with fecal metagenomic sequencing between 6-weeks to 2-years postpartum (481 samples). ASD-related social development was assessed with the Social Responsiveness Scale (SRS-2). Linear regression, PERMANOVA, and Microbiome Multivariable Association with Linear Models (MaAsLin2) were adjusted for sociodemographic factors. Stratified models estimated sex-specific effects.
Genes encoding pathways for synthesis of short-chain fatty acids were associated with higher SRS-2 scores, indicative of ASDs. Fecal concentrations of butyrate were also positively associated with ASD-related SRS-2 scores, some of which may be explained by formula use.
The distribution of age at outcome assessment differed in the cohorts included, potentially limiting comparability between cohorts. Stool sample collection methods also differed between cohorts. Our study population reflects the general U.S. population, and thus includes few participants who met the criteria for being at high risk of developing ASD.
Our study is among the first multicenter studies in the U.S. to describe prospective microbiome development from infancy in relation to neurodevelopment associated with ASDs. Our work contributes to clarifying which microbial features associate with subsequent diagnosis of neuropsychiatric outcomes. This will allow for future interventional research targeting the microbiome to change neurodevelopmental trajectories.
识别自闭症谱系障碍（ASD）的可改变风险因素可以为减少经济负担的干预措施提供信息。婴儿/幼儿肠道微生物组是与社交行为相关的一个特征，但在不同队列中的结果有所不同。我们旨在确定生命早期肠道微生物组与自闭症相关行为之间一致的总体和性别特异性关联。
利用美国（美国）儿科队列的环境对儿童健康结果的影响（ECHO）联盟，我们收集了 304 名参与者的粪便宏基因组测序数据，这些参与者在产后 6 周到 2 岁之间（481 个样本）。使用社交反应量表（SRS-2）评估 ASD 相关的社会发育情况。线性回归、PERMANOVA 和微生物组多变量与线性模型（MaAsLin2）调整了社会人口统计学因素。分层模型估计了性别特异性效应。
编码短链脂肪酸合成途径的基因与 SRS-2 评分较高相关，提示 ASD。粪便中丁酸盐的浓度也与 ASD 相关的 SRS-2 评分呈正相关，其中一些可能与配方奶的使用有关。
纳入的队列中结局评估的年龄分布不同，可能限制了队列之间的可比性。粪便样本采集方法也在不同的队列之间有所不同。我们的研究人群反映了一般的美国人群，因此包括很少符合发展为 ASD 高风险标准的参与者。
我们的研究是美国首批描述与 ASD 相关的神经发育相关的从婴儿期开始的前瞻性微生物组发展的多中心研究之一。我们的工作有助于阐明哪些微生物特征与随后的神经精神结局诊断相关。这将为未来针对微生物组的干预性研究提供改变神经发育轨迹的机会。
