De Marzio Margherita, Lasky-Su Jessica, Chu Su H, Prince Nicole, Litonjua Augusto A, Weiss Scott T, Kelly Rachel S, Glass Kimberly R
bioRxiv. 2023 Jul 15:2023.06.23.546277. doi: 10.1101/2023.06.23.546277.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with various proposed environmental risk factors and a rapidly increasing prevalence. Mounting evidence suggests a potential role of vitamin D deficiency in ASD pathogenesis, though the causal mechanisms remain largely unknown. Here we investigate the impact of vitamin D on child neurodevelopment through an integrative network approach that combines metabolomic profiles, clinical traits, and neurodevelopmental data from a pediatric cohort. Our results show that vitamin D deficiency is associated with changes in the metabolic networks of tryptophan, linoleic, and fatty acid metabolism. These changes correlate with distinct ASD-related phenotypes, including delayed communication skills and respiratory dysfunctions. Additionally, our analysis suggests the kynurenine and serotonin sub-pathways may mediate the effect of vitamin D on early childhood communication development. Altogether, our findings provide metabolome-wide insights into the potential of vitamin D as a therapeutic option for ASD and other communication disorders.
自闭症谱系障碍(ASD)是一种神经发育障碍,有多种潜在的环境风险因素,且患病率正在迅速上升。越来越多的证据表明维生素D缺乏在ASD发病机制中可能起作用,但其因果机制在很大程度上仍不清楚。在这里,我们通过一种综合网络方法来研究维生素D对儿童神经发育的影响,该方法结合了来自儿科队列的代谢组学特征、临床特征和神经发育数据。我们的结果表明,维生素D缺乏与色氨酸、亚油酸和脂肪酸代谢的代谢网络变化有关。这些变化与不同的ASD相关表型相关,包括沟通技能延迟和呼吸功能障碍。此外,我们的分析表明,犬尿氨酸和血清素子途径可能介导维生素D对幼儿沟通发展的影响。总之,我们的研究结果提供了全代谢组范围的见解,以了解维生素D作为ASD和其他沟通障碍治疗选择的潜力。