Department of Pediatrics, Chang Gung Memorial Hospital at Keelung, Chang Gung University, Taoyuan, Taiwan.
Community Medicine Research Centre, Chang Gung Memorial Hospital, Keelung, Taiwan.
Pediatr Allergy Immunol. 2018 Aug;29(5):496-503. doi: 10.1111/pai.12909. Epub 2018 Jun 5.
Several metabolites and altered metabolic pathways have been reported to be associated with asthma. However, longitudinal analysis of the dynamics of metabolites contributing to the development of asthma has not yet been fully clarified.
We sought to identify the metabolic mechanisms underlying asthma development in early childhood. Thirty children with asthma and paired healthy controls from a prospective birth cohort were enrolled. Time series analysis of urinary metabolites collected at ages 1, 2, 3, and 4 years was assessed using H nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA). Metabolites identified were studied in relation to changes over time in a linear mixed model for repeated measures.
A total of 172 urine samples collected from the enrolled children were analyzed. Urinary metabolomics identified four metabolites significantly associated with childhood asthma development, with longitudinal analysis. Among them, dimethylamine, a metabolite produced by intestinal bacteria, appeared to shift from higher to lower level during asthma development. A persistent lower level of 1-methylnicotinamide and allantoin was found in children with asthma, with a peak difference at age 3 years (P = .032 and P = .021, respectively). Furthermore, a significant inverse correlation was found between allantoin and house dust mite sensitization (Spearman's r = -.297 P = .035).
Longitudinal urinary metabolomic profiling provides a link of microbe-environment interactions in the development of childhood asthma. 1-Methylnicotinamide and allantoin may participate in allergic reactions in response to allergen exposure, potentially serving as specific biomarkers for asthma.
有报道称，几种代谢物和代谢途径的改变与哮喘有关。然而，导致哮喘发展的代谢物的动态变化的纵向分析尚未完全阐明。
我们试图确定儿童早期哮喘发展的代谢机制。从一个前瞻性出生队列中招募了 30 名哮喘儿童和配对的健康对照者。使用 H 核磁共振（NMR）光谱结合偏最小二乘判别分析（PLS-DA）对 1、2、3 和 4 岁时收集的尿液代谢物进行时间序列分析。在用于重复测量的线性混合模型中，研究了与随时间变化相关的代谢物。
对纳入儿童的 172 个尿液样本进行了分析。尿液代谢组学鉴定出 4 种与儿童哮喘发展相关的代谢物，具有纵向分析。其中，二甲基胺是肠道细菌产生的代谢物，在哮喘发展过程中似乎从高水平变为低水平。在哮喘儿童中发现 1-甲基烟酰胺和尿囊素的水平持续较低，在 3 岁时达到峰值差异（P =.032 和 P =.021）。此外，尿囊素与屋尘螨致敏之间存在显著的负相关（Spearman r = -.297，P =.035）。
纵向尿液代谢组学分析为儿童哮喘发展中微生物-环境相互作用提供了联系。1-甲基烟酰胺和尿囊素可能参与了对过敏原暴露的过敏反应，可能作为哮喘的特异性生物标志物。
