Urinary N-methylnicotinamide and β-aminoisobutyric acid predict catch-up growth in undernourished Brazilian children.
Urinary N-methylnicotinamide and β-aminoisobutyric acid predict catch-up growth in undernourished Brazilian children.
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DOI：
10.1038/srep19780
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发表时间：
2016-01-27
影响因子：
4.6
通讯作者：
Swann JR
中科院分区：
文献类型：
--
作者：
Mayneris-Perxachs J;Lima AA;Guerrant RL;Leite ÁM;Moura AF;Lima NL;Soares AM;Havt A;Moore SR;Pinkerton R;Swann JR
儿童早期的肠道感染、肠病和营养不良是儿童死亡、神经发育受损和以后代谢疾病的可预防危险因素。然而，将这些暴露和结果联系起来的机制仍有待阐明，用于识别处于危险中的儿童的生物标志物也有待阐明。通过检查参与巴西半干旱地区病例对照研究的营养和营养不良儿童的尿液代谢表型，我们发现了与机制、生物标志物和结果潜在相关的关键差异。研究发现，营养不良会扰乱多种生化途径，包括胆碱和色氨酸代谢，同时还会增加肠道微生物组的蛋白水解活性。此外，在营养不良的儿童中观察到代谢适应减少了能量消耗，这反映在 N-甲基烟酰胺增加和 β-氨基异丁酸排泄减少。有趣的是，在几个月前，那些营养不良的儿童就观察到了加速的追赶性生长，表现出更强劲的代谢适应。因此，尿液中的 N-甲基烟酰胺和 β-氨基异丁酸是预测营养不良儿童短期生长结果和识别注定会进一步生长不足的儿童的有前途的生物标志物。这些发现对于了解早期营养不良长期后遗症的影响因素（包括认知、生长和代谢功能）具有重要意义。
Enteric infections, enteropathy and undernutrition in early childhood are preventable risk factors for child deaths, impaired neurodevelopment, and later life metabolic diseases. However, the mechanisms linking these exposures and outcomes remain to be elucidated, as do biomarkers for identifying children at risk. By examining the urinary metabolic phenotypes of nourished and undernourished children participating in a case-control study in Semi-Arid Brazil, we identified key differences with potential relevance to mechanisms, biomarkers and outcomes. Undernutrition was found to perturb several biochemical pathways, including choline and tryptophan metabolism, while also increasing the proteolytic activity of the gut microbiome. Furthermore, a metabolic adaptation was observed in the undernourished children to reduce energy expenditure, reflected by increased N-methylnicotinamide and reduced β-aminoisobutyric acid excretion. Interestingly, accelerated catch-up growth was observed in those undernourished children displaying a more robust metabolic adaptation several months earlier. Hence, urinary N-methylnicotinamide and β-aminoisobutyric acid represent promising biomarkers for predicting short-term growth outcomes in undernourished children and for identifying children destined for further growth shortfalls. These findings have important implications for understanding contributors to long-term sequelae of early undernutrition, including cognitive, growth, and metabolic functions.