Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea.
Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea.
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DOI：
10.1371/journal.pone.0192092
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Swann JR
中科院分区：
文献类型：
--
作者：
Farràs M;Chandwe K;Mayneris-Perxachs J;Amadi B;Louis-Auguste J;Besa E;Zyambo K;Guerrant R;Kelly P;Swann JR
环境性肠功能障碍（EED）在整个热带地区普遍存在，在儿童中与发育迟缓和其他不良健康结果有关。EED的特征之一是绒毛损伤。在患有严重急性营养不良（SAM）的儿童中，肠病的严重程度更大，短期死亡率很高，但肠病的代谢后果尚不清楚。在这里，我们描述了与赞比亚严重营养不良儿童的绒毛健康、经典肠病生物标志物和人体测量测量相关的尿代谢改变。我们分析了赞比亚20名6至23个月的急性营养不良住院儿童。对小肠活检进行组织学评估（n = 15），收集人体测量和肠道功能测量数据，并通过1H核磁共振（NMR）谱分析代谢表型。不能对社区对照儿童进行内窥镜检查。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渗透性生物标志物呈负相关（p = 0.000和p = 0.015）。绒毛高度较短与肠道微生物代谢、能量代谢和肌肉代谢相关代谢物丰度降低相关（p = 0.034）。绒毛变钝也与蔗糖排泄量增加有关（p = 0.013）。在严重营养不良的住院儿童中，肠绒毛变钝与几种代谢紊乱有关。这些改变包括肌肉代谢的改变，强化了EED与生长迟缓之间的联系，以及肠道微生物群与宿主之间生化交换的中断。这些发现扩展了我们对绒毛钝化的下游后果的理解，并提供了新的非侵入性肠病功能障碍生物标志物。本研究的主要局限性是缺乏比较对照组和肠道微生物群特征。
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. 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). 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.
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影响因子：
3.7
作者：
Guerrant RL;Leite AM;Pinkerton R;Medeiros PH;Cavalcante PA;DeBoer M;Kosek M;Duggan C;Gewirtz A;Kagan JC;Gauthier AE;Swann J;Mayneris-Perxachs J;Bolick DT;Maier EA;Guedes MM;Moore SR;Petri WA;Havt A;Lima IF;Prata MM;Michaleckyj JC;Scharf RJ;Sturgeon C;Fasano A;Lima AA
通讯作者：
Lima AA
影响因子：
3.8
作者：
Kelly P;Besa E;Zyambo K;Louis-Auguste J;Lees J;Banda T;Soko R;Banda R;Amadi B;Watson A
通讯作者：
Watson A
影响因子：
11.1
作者：
Amadi B;Besa E;Zyambo K;Kaonga P;Louis-Auguste J;Chandwe K;Tarr PI;Denno DM;Nataro JP;Faubion W;Sailer A;Yeruva S;Brantner T;Murray J;Prendergast AJ;Turner JR;Kelly P
通讯作者：
Kelly P
影响因子：
11.8
作者：
Keusch, Gerald T.;Denno, Donna M.;Brewer, Thomas
通讯作者：
Brewer, Thomas
影响因子：
168.9
作者：
Black, Robert E.;Victora, Cesar G.;Uauy, Ricardo
通讯作者：
Uauy, Ricardo