Department of Microbiology and Cell Science, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32603, USA.
School of Science and Technology, Örebro University, Örebro 702 81, Sweden.
Cell. 2024 Apr 11;187(8):1853-1873.e15. doi: 10.1016/j.cell.2024.02.035. Epub 2024 Apr 3.
This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.
这项研究对一个出生队列进行了超过 20 年的跟踪,以寻找与神经发育障碍(ND)诊断相关的因素。详细的、生命早期的纵向问卷捕捉了感染和抗生素事件、压力、产前因素、家族史等。评估了包括脐带血清代谢组和脂质组、人类白细胞抗原(HLA)基因型、婴儿微生物组和粪便代谢组在内的生物标志物。在随访时间跨越的 16440 名瑞典儿童中,有 1197 名患有 ND。总体上以及特定的 ND 亚型(包括智力残疾、言语障碍、注意缺陷/多动障碍和自闭症)未来 ND 诊断存在显著关联。这项研究揭示了微生物组与未来诊断的联系,以及早期出现的情绪和胃肠道问题。这些发现表明与免疫失调和代谢有关,加上压力、生命早期感染和抗生素的作用。在这项针对大规模人群的前瞻性、纵向研究中,婴儿生物标志物和风险因素的汇聚为神经发育的早期预测和干预奠定了基础。