Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA, United States; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, United States.
Department of Pediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
J Nutr. 2024 Feb;154(2):403-411. doi: 10.1016/j.tjnut.2023.12.011. Epub 2023 Dec 11.
Provision of zinc supplementation to young children has been associated with reduced infectious morbidity and better growth outcomes. However, the metabolic pathways underlying these outcomes are unclear, and metabolomic data from humans undergoing zinc supplementation, particularly infants, are generally lacking.
This study aimed to examine the effect of zinc supplementation on metabolic profiles in Tanzanian infants aged 6 wk and 6 mo.
Blood samples were collected at age 6 wk and 6 mo from 50 Tanzanian infants who were enrolled in a randomized placebo-controlled trial of zinc supplementation (5 mg oral daily). Metabolomic analysis using an ultrahigh-performance liquid chromatography/tandem mass spectroscopy platform was performed to identify potential metabolomic profiles and biomarkers associated with zinc supplementation. Principal component analysis (PCA) was used to summarize metabolomic data from all samples. Two-way repeated measures analysis of variance with compound symmetry covariance structures were used to compare metabolome levels over time between infants in the 2 treatment arms.
In PCA, the samples tended to be more separated by child age (6 wk compared with 6 mo) than by zinc supplementation status. We found that zinc supplementation affected a variety of metabolites associated with amino acid, lipid, nucleotide, and xenobiotic metabolism, including indoleacetate in the tryptophan metabolism pathway; 3-methoxytrosine and 4-hydrxoyphenylphruvate in the tyrosine pathway; eicosanedioate, 2-aminooctanoate, and N-acetyl-2-aminooctanoate in the fatty acid pathway; and N6-succinyladenosine in the purine metabolism pathway. Compared to the relatively small number of metabolites associated with zinc supplements, many infant metabolites changed significantly from age 6 wk to 6 mo.
Zinc supplementation, despite having overall clinical benefits, appears to induce limited metabolomic changes in blood metabolites in young infants. Future larger studies may be warranted to further examine metabolic pathways associated with zinc supplementation. The parent trial was registered at clinicaltrials.gov as NCT00421668.
向幼儿提供锌补充剂与降低传染性发病率和更好的生长结果有关。然而，这些结果的代谢途径尚不清楚，并且接受锌补充剂的人体（特别是婴儿）的代谢组学数据通常缺乏。
本研究旨在检查锌补充剂对坦桑尼亚 6 周和 6 个月大婴儿代谢谱的影响。
从参加锌补充剂（5mg 口服每日）随机安慰剂对照试验的 50 名坦桑尼亚婴儿中收集了 6 周和 6 个月时的血液样本。使用超高效液相色谱/串联质谱平台进行代谢组学分析，以鉴定与锌补充相关的潜在代谢组学特征和生物标志物。主成分分析（PCA）用于总结所有样品的代谢组学数据。使用具有复合对称协方差结构的双向重复测量方差分析比较 2 种治疗臂中婴儿随时间的代谢水平。
在 PCA 中，样本的分离更多地取决于儿童年龄（6 周与 6 个月），而不是锌补充剂状态。我们发现，锌补充剂影响了多种与氨基酸、脂质、核苷酸和外源性代谢物相关的代谢物，包括色氨酸代谢途径中的吲哚乙酸；酪氨酸途径中的 3-甲氧基酪氨酸和 4-羟苯丙酮酸；脂肪酸途径中的二十烷二酸、2-氨基辛酸和 N-乙酰-2-氨基辛酸；嘌呤代谢途径中的 N6-琥珀酰腺苷。与与锌补充剂相关的代谢物数量相对较少相比，许多婴儿代谢物从 6 周龄到 6 月龄发生了明显变化。
尽管锌补充剂具有总体临床益处，但似乎会引起幼儿血液代谢物的代谢组学变化有限。未来可能需要更大的研究进一步检查与锌补充相关的代谢途径。该母试验在 clinicaltrials.gov 上注册为 NCT00421668。
