Impaired Barrier Function and Autoantibody Generation in Malnutrition Enteropathy in Zambia.
Impaired Barrier Function and Autoantibody Generation in Malnutrition Enteropathy in Zambia.
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DOI：
10.1016/j.ebiom.2017.07.017
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发表时间：
2017-08
期刊：
影响因子：
11.1
通讯作者：
Kelly P
中科院分区：
文献类型：
--
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
营养不良造成的肠道损害对全球成千上万儿童的生存构成威胁。我们对赞比亚卢萨卡患有严重急性营养不良(SAM)和持续性腹泻的儿童进行了研究，方法包括内窥镜检查、活检以及血液和肠道分泌物中标志物和保护蛋白的分析。我们在看似健康的成年人中进行了平行研究，并只在看似健康的儿童中分析了生物标记物。绒毛高度和隐窝深度在儿童和成人对照组中无差异，但儿童SAM组上皮表面减少(中位数445，四分位数范围(IQR388,562μm/100gμm肌肉粘膜)与成人(578，IQR465,709；P=0.004)。组织学损害和Claudin-4和E-cadherin的破坏在SAM儿童中最为明显。作为细菌易位标志的循环脂多糖，营养不良儿童(251IQR110,460Eu/ml)高于健康儿童(51，IQR0111；P=0.0001)。其他易位标记也显示出类似的模式。抗去胺化醇溶蛋白多肽Ig G水平虽在正常范围内，但儿童SAM组(中位数2.7U/ml，IQR1.5-8.6)高于成人组(1.6，1.4-2.1；P=0.005)，且与绒毛高度呈负相关(ρ=−=0.79，n=0.13，P=0.001)。营养不良肠病与肠道屏障功能障碍和免疫失调有关。严重急性营养不良儿童的肠病以可变绒毛钝化和上皮破坏为特征。生物标志物表明微生物从肠腔到体循环的移位水平非常高。腹腔型自身抗体与绒毛钝化、微生物易位标志物和死亡率相关。有大量证据表明，在许多低收入和中等收入国家，儿童营养不良是死亡率的一个主要因素。死亡率仍然高得令人无法接受。在这里，我们显示了严重的急性营养不良的特征是非常高水平的微生物移位和炎症，以及严重的粘膜损伤和紧密连接蛋白表达紊乱。抗组织转谷氨酰胺酶和去胺化醇溶蛋白多肽的抗体虽然在正常范围内，但与绒毛形态、易位标志物和死亡相关。营养不良肠病导致粘膜炎症、微生物移位和免疫失调。
Intestinal damage in malnutrition constitutes a threat to the survival of many thousands of children globally. We studied children in Lusaka, Zambia, with severe acute malnutrition (SAM) and persistent diarrhea using endoscopy, biopsy and analysis of markers and protective proteins in blood and intestinal secretions. We carried out parallel investigations in apparently healthy adults, and analyzed biomarkers only in apparently healthy children. Villus height and crypt depth did not differ in children with SAM and adult controls, but epithelial surface was reduced in children with SAM (median 445, interquartile range (IQR) 388, 562 μm per 100 μm muscularis mucosae) compared to adults (578, IQR 465,709; P = 0.004). Histological lesions and disruptions of claudin-4 and E-cadherin were most pronounced in children with SAM. Circulating lipopolysaccharide, a marker of bacterial translocation, was higher in malnourished children (251, IQR 110,460 EU/ml) than in healthy children (51, IQR 0,111; P = 0.0001). Other translocation markers showed similar patterns. Anti-Deamidated Gliadin Peptide IgG concentrations, although within the normal range, were higher in children with SAM (median 2.7 U/ml, IQR 1.5–8.6) than in adults (1.6, 1.4–2.1; P = 0.005), and were inversely correlated with villus height (ρ = − 0.79, n = 13, P = 0.001). Malnutrition enteropathy is associated with intestinal barrier failure and immune dysregulation. Enteropathy in children with severe acute malnutrition is characterized by variable villus blunting and epithelial disruption. Biomarkers indicate very high levels of microbial translocation from intestinal lumen to systemic circulation. Coeliac-type autoantibodies were associated with villus blunting, microbial translocation markers and mortality. There is abundant evidence that childhood malnutrition is a major contributor to mortality in many low and middle income countries. Mortality remains unacceptably high. Here we show that severe acute malnutrition was characterized by very high levels of microbial translocation and inflammation, and severe mucosal damage with disturbed tight junction protein expression. Antibodies to tissue transglutaminase and deamidated gliadin peptides, although within the normal range, correlated with villus morphology, translocation markers and death. Malnutrition enteropathy permits mucosal inflammation, microbial translocation and immune dysregulation.
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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：
Kosek MN;MAL-ED Network Investigators
通讯作者：
MAL-ED Network Investigators
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：
24.5
作者：
Menzies, IS;Zuckerman, MJ;Gregory, GG
通讯作者：
Gregory, GG
影响因子：
3.6
作者：
Campbell, DI;Murch, SH;Lunn, PG
通讯作者：
Lunn, PG