Computational and Systems Medicine Group, Division of Surgery and Cancer, Imperial College, London, United Kingdom.
CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Barcelona, Spain.
PLoS One. 2018 Mar 2;13(3):e0192092. doi: 10.1371/journal.pone.0192092. eCollection 2018.
Environmental enteric dysfunction (EED) is widespread throughout the tropics and in children is associated with stunting and other adverse health outcomes. One of the hallmarks of EED is villus damage. In children with severe acute malnutrition (SAM) the severity of enteropathy is greater and short term mortality is high, but the metabolic consequences of enteropathy are unknown. Here, we characterize the urinary metabolic alterations associated with villus health, classic enteropathy biomarkers and anthropometric measurements in severely malnourished children in Zambia.
METHODS/PRINCIPAL FINDINGS: We analysed 20 hospitalised children with acute malnutrition aged 6 to 23 months in Zambia. Small intestinal biopsies were assessed histologically (n = 15), anthropometric and gut function measurements were collected and the metabolic phenotypes were characterized by 1H nuclear magnetic resonance (NMR) spectroscopy. Endoscopy could not be performed on community controls children. Growth parameters were inversely correlated with enteropathy biomarkers (p = 0.011) and parameters of villus health were inversely correlated with translocation and permeability biomarkers (p = 0.000 and p = 0.015). Shorter villus height was associated with reduced abundance of metabolites related to gut microbial metabolism, energy and muscle metabolism (p = 0.034). Villus blunting was also related to increased sucrose excretion (p = 0.013).
CONCLUSIONS/SIGNIFICANCE: Intestinal villus blunting is associated with several metabolic perturbations in hospitalized children with severe undernutrition. Such alterations include altered muscle metabolism, reinforcing the link between EED and growth faltering, and a disruption in the biochemical exchange between the gut microbiota and host. These findings extend our understanding on the downstream consequences of villus blunting and provide novel non-invasive biomarkers of enteropathy dysfunction. The major limitations of this study are the lack of comparative control group and gut microbiota characterization.
环境肠道功能障碍（EED）在整个热带地区广泛存在，与儿童发育迟缓及其他不良健康结果有关。EED 的一个标志是绒毛损伤。患有严重急性营养不良（SAM）的儿童中，肠病的严重程度更高，短期死亡率也更高，但肠病的代谢后果尚不清楚。在这里，我们描述了赞比亚严重营养不良儿童与绒毛健康、经典肠病生物标志物和人体测量学测量相关的尿代谢改变。
方法/主要发现：我们分析了赞比亚 20 名 6 至 23 个月大的急性营养不良住院儿童。对 15 名儿童进行了小肠活检的组织学评估，收集了人体测量和肠道功能测量数据，并通过 1H 核磁共振（NMR）光谱对代谢表型进行了特征描述。由于内镜检查无法在社区对照儿童中进行。生长参数与肠病生物标志物呈负相关（p = 0.011），绒毛健康参数与易位和通透性生物标志物呈负相关（p = 0.000 和 p = 0.015）。较短的绒毛高度与与肠道微生物代谢、能量和肌肉代谢相关的代谢物丰度降低有关（p = 0.034）。绒毛变钝也与蔗糖排泄增加有关（p = 0.013）。
结论/意义：在患有严重营养不良的住院儿童中，肠绒毛变钝与多种代谢紊乱有关。这些改变包括肌肉代谢改变，这加强了 EED 与生长迟缓的联系，以及肠道微生物群和宿主之间生化交换的中断。这些发现扩展了我们对绒毛变钝的下游后果的理解，并提供了肠病功能障碍的新型非侵入性生物标志物。本研究的主要局限性是缺乏对照组和肠道微生物群特征。
