Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
Department of Pediatrics, University of Washington, Seattle, WA, United States.
Am J Clin Nutr. 2024 Sep;120 Suppl 1:S84-S93. doi: 10.1016/j.ajcnut.2024.02.026.
Environmental Enteric Dysfunction (EED) is an acquired disorder of asymptomatic altered gut function, the etiology of which is unknown. EED is postulated to be a major contributor to growth faltering in early childhood in regions where early-life enteropathogenic carriage is prevalent. Few studies have examined the critical organ (the upper small bowel) with enteropathogens in the evolution of small bowel disease.
The objective of this study was to determine if fecal enteropathogenic detection predicts subsequent EED histology.
Fecal samples were obtained from undernourished children aged <2 y without diarrhea enrolled in 3 cohort studies, who failed nutritional intervention and subsequently underwent endoscopy. Duodenal biopsies from 245 (Bangladesh n = 120, Pakistan n = 57, and Zambia n = 68) children were scored using a semiquantitative histologic grading protocol. Thirteen enteropathogens were sought in common across the 3 centers using TaqMan array cards (TAC) (Bangladesh and Pakistan) and the Luminex platform (Zambia). An additional 18 pathogens and 32 virulence loci were sought by TAC and included in sensitivity analyses restricted to TAC data.
Multivariable linear regressions adjusting for study center, age at stool collection, and stool-to-biopsy interval demonstrated the following: 1) an association of norovirus and Shigella detection with subsequent enterocyte injury [β 0.2 (95% CI: 0.1, 0.3); P = 0.002 and β 0.2 (95% CI: 0.0, 0.3); P = 0.008, respectively], 2) association of Campylobacter with intraepithelial lymphocytes [β 0.2 (95% CI: 0.0, 0.4); P = 0.046], and 3) association of Campylobacter and enterotoxigenic Escherichia coli with a summative EED histopathology index score [β 4.2 (95% CI: 0.8, 7.7); P = 0.017 and β 3.9 (95% CI: 0.5, 7.3); P = 0.027, respectively]. All but 2 of these associations (Shigella-enterocyte injury and Campylobacter-index score) were also demonstrated in TAC-only sensitivity analyses, which identified additional associations between other pathogens, pathogen burden, or virulence loci primarily with the same histologic parameters.
The detection of some enteropathogens in asymptomatic infections is associated with subsequent EED histopathology. These novel findings offer a basis for future EED etiology and pathogenesis studies.
环境肠道功能障碍（EED）是一种无症状的肠道功能改变的获得性疾病，其病因尚不清楚。据推测，在早期生活中肠道病原体携带普遍的地区，EED 是导致儿童早期生长迟缓的主要因素之一。很少有研究检查过有肠道病原体存在的关键器官（上小肠）在小肠疾病演变中的作用。
本研究旨在确定粪便肠道病原体检测是否可预测随后的 EED 组织学表现。
从 3 项队列研究中招募了 3 名患有营养不良且年龄小于 2 岁的无腹泻儿童，收集了粪便样本。这些儿童未能通过营养干预得到改善，随后接受了内镜检查。使用半定量组织学评分方案对来自 245 名儿童（孟加拉国 n = 120、巴基斯坦 n = 57 和赞比亚 n = 68）的十二指肠活检进行评分。使用 TaqMan 阵列卡（TAC）（孟加拉国和巴基斯坦）和 Luminex 平台（赞比亚）在 3 个中心检测了 13 种常见的肠道病原体。通过 TAC 还检测了另外 18 种病原体和 32 个毒力基因座，并将其纳入仅针对 TAC 数据的敏感性分析中。
多变量线性回归分析调整了研究中心、粪便采集时的年龄和粪便与活检的时间间隔，结果显示：1）诺如病毒和志贺菌检测与随后的肠细胞损伤相关[β 0.2（95%CI：0.1，0.3）；P = 0.002 和β 0.2（95%CI：0.0，0.3）；P = 0.008]，2）弯曲菌与上皮内淋巴细胞相关[β 0.2（95%CI：0.0，0.4）；P = 0.046]，3）弯曲菌和肠毒性大肠杆菌与 EED 组织病理学综合指数评分相关[β 4.2（95%CI：0.8，7.7）；P = 0.017 和β 3.9（95%CI：0.5，7.3）；P = 0.027]。除了 Shigella-肠细胞损伤和 Campylobacter-index 评分这两个关联（这两个关联仅在 TAC 敏感性分析中得到证实）之外，所有这些关联在 TAC 仅有的敏感性分析中也得到了证实，该分析还确定了其他病原体、病原体负担或毒力基因座与相同组织学参数之间的其他关联。
在无症状感染中检测到某些肠道病原体与随后的 EED 组织病理学表现有关。这些新发现为未来的 EED 病因和发病机制研究提供了依据。
