Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting.
Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting.
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DOI：
10.1038/s41564-020-00849-w
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发表时间：
2021-04
影响因子：
28.3
通讯作者：
Kelly P
中科院分区：
文献类型：
--
作者：
Amadi B;Zyambo K;Chandwe K;Besa E;Mulenga C;Mwakamui S;Siyumbwa S;Croft S;Banda R;Chipunza M;Chifunda K;Kazhila L;VanBuskirk K;Kelly P
环境性肠病是非洲和南亚数百万儿童生长缓慢的主要原因。我们在赞比亚卢萨卡对 297 名发育迟缓儿童（招募时 2-17 个月大）和 46 名生长良好的对照儿童（招募时 1-5 个月大）进行了一项纵向、观察性和干预性研究。对照儿童仅在基线时提供数据。每天为儿童提供玉米粉-大豆混合物、鸡蛋和微量营养素粉的营养补充，并随访至 24 个月大。营养补充4-6个月后生长没有改善的儿童被归类为无反应性发育迟缓。我们通过测量基线时和宣布无反应时的循环脂多糖 (LPS)、LPS 结合蛋白和可溶性 CD14，监测无反应性发育迟缓队列 (n = 108) 中微生物从肠腔到血流的易位。我们发现，微生物易位随着年龄的增长而减少，尽管存在持续的病原体压力和持续的肠上皮损伤，但 108 名无反应性发育迟缓儿童中，有 81 名 (75%) 的 LPS 下降。我们使用共焦激光内窥镜检查发现粘膜渗漏也随着年龄的增长而下降。然而，肠活检中刷状缘酶、营养转运蛋白和粘膜屏障基因的表达不随年龄变化或与微生物易位的生物标志物相关。我们认为环境性肠病是通过适应病原体介导的上皮损伤而产生的。尽管环境性肠病可减少微生物易位，但其代价是生长受损。绒毛变钝造成的上皮表面积减少可以解释这些发现。研究赞比亚营养不良且持续发育迟缓的儿童的肠道病理学表明，生命早期对病原体暴露的适应可能解释了为什么发育迟缓的儿童对营养补充反应不佳。
Environmental enteropathy is a major contributor to growth faltering in millions of children in Africa and South Asia. We carried out a longitudinal, observational and interventional study in Lusaka, Zambia, of 297 children with stunting (aged 2–17 months at recruitment) and 46 control children who had good growth (aged 1–5 months at recruitment). Control children contributed data only at baseline. Children were provided with nutritional supplementation of daily cornmeal-soy blend, an egg and a micronutrient sprinkle, and were followed up to 24 months of age. Children whose growth did not improve over 4–6 months of nutritional supplementation were classified as having non-responsive stunting. We monitored microbial translocation from the gut lumen to the bloodstream in the cohort with non-responsive stunting (n = 108) by measuring circulating lipopolysaccharide (LPS), LPS-binding protein and soluble CD14 at baseline and when non-response was declared. We found that microbial translocation decreased with increasing age, such that LPS declined in 81 (75%) of 108 children with non-responsive stunting, despite sustained pathogen pressure and ongoing intestinal epithelial damage. We used confocal laser endomicroscopy and found that mucosal leakiness also declined with age. However, expression of brush border enzyme, nutrient transporter and mucosal barrier genes in intestinal biopsies did not change with age or correlate with biomarkers of microbial translocation. We propose that environmental enteropathy arises through adaptation to pathogen-mediated epithelial damage. Although environmental enteropathy reduces microbial translocation, it does so at the cost of impaired growth. The reduced epithelial surface area imposed by villus blunting may explain these findings. Studying the intestinal pathology of undernourished children in Zambia with persistent stunting reveals that adaptation to pathogen exposure in early life may explain why children with stunting do not respond well to nutrient supplementation.
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