Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, United States.
Am J Clin Nutr. 2024 Sep;120 Suppl 1:S73-S83. doi: 10.1016/j.ajcnut.2024.02.029.
Validated biomarkers could catalyze environmental enteric dysfunction (EED) research.
Leveraging an EED histology scoring system, this multicountry analysis examined biomarker associations with duodenal histology features among children with EED. We also examined differences in 2-h compared with 1-h urine collections in the lactulose rhamnose (LR) dual sugar test.
Three cohorts of undernourished children unresponsive to nutrition intervention underwent esophagogastroduodenoscopy and duodenal biopsies. Histopathology scores were compared to fecal calprotectin (CAL), myeloperoxidase (MPO), neopterin (NEO), and urinary LR ratio and lactulose percentage recovery. Log-transformed biomarkers were used in linear regressions adjusted for age, center, and sample collection-biopsy time interval in multivariable models.
Data on >1 biomarker were available for 120 Bangladeshi (CAL, MPO, NEO, and LR), 63 Pakistani (MPO, NEO, and LR), and 63 Zambian children (CAL). Median age at endoscopy was similar (19 mo) across centers. Median sample collection prior to endoscopy was consistent with each center's study design: 2 wk in Bangladesh (urine and stool) and Zambia (stool), and 6 (urine) and 11 (stool) mo in Pakistan. In multivariable models, intraepithelial lymphocytes were associated with CAL (exponentiated [exp.] coefficient: 1.19; 95% confidence interval [CI]: 1, 1.41), intramucosal Brunner's glands with MPO (exp. coefficient: 1.33; 95% CI: 1.05, 1.69) and NEO (exp. coefficient: 1.37; 95% CI: 1.1, 1.7), and chronic inflammation with NEO (exp. coefficient: 1.61; 95% CI: 1.17, 2.17). Intraepithelial lymphocytes were associated with lactulose % recovery (exp. coefficient: 1.22; 95% CI: 1.05, 1.41). LR recovery was substantially lower in 1-h collections than in 2-h collections.
Four commonly used markers of enteric dysfunction were associated with specific histologic features. One-hour urine collection may be insufficient to reflect small bowel permeability in LR testing. While acknowledging the challenges with obtaining relevant tissue, these findings form the basis for further EED biomarker validation research.
经过验证的生物标志物可以推动肠病相关的环境因素研究。
本项多中心研究利用肠病相关的组织学评分系统，分析了在患有肠病相关环境因素的儿童中，生物标志物与十二指肠组织学特征之间的关联。我们还比较了乳果糖-鼠李糖（LR）双糖试验中 2 小时与 1 小时尿液收集的差异。
三组营养不良且对营养干预无反应的儿童接受了食管胃十二指肠镜检查和十二指肠活检。组织病理学评分与粪便钙卫蛋白（CAL）、髓过氧化物酶（MPO）、新蝶呤（NEO）和尿 LR 比值以及乳果糖回收率进行比较。在多变量模型中，对年龄、中心和样本采集-活检时间间隔进行了调整，使用对数转换后的生物标志物进行线性回归。
120 名孟加拉国儿童（CAL、MPO、NEO 和 LR）、63 名巴基斯坦儿童（MPO、NEO 和 LR）和 63 名赞比亚儿童（CAL）的生物标志物数据超过 1 种。内窥镜检查时的中位年龄在各中心之间相似（19 个月）。样本采集的中位数时间与每个中心的研究设计一致：孟加拉国（尿液和粪便）和赞比亚（粪便）为 2 周，巴基斯坦（尿液）和（粪便）为 6 个月和 11 个月。在多变量模型中，上皮内淋巴细胞与 CAL 相关（指数[Exp.]系数：1.19；95%置信区间[CI]：1.01，1.41），固有层布兰纳氏腺与 MPO（Exp.系数：1.33；95% CI：1.05，1.69）和 NEO（Exp.系数：1.37；95% CI：1.10，1.7），慢性炎症与 NEO 相关（Exp.系数：1.61；95% CI：1.17，2.17）。上皮内淋巴细胞与乳果糖回收率相关（Exp.系数：1.22；95% CI：1.05，1.41）。1 小时收集的 LR 回收率明显低于 2 小时收集的。
四种常用的肠功能障碍标志物与特定的组织学特征相关。在 LR 检测中，1 小时的尿液收集可能不足以反映小肠通透性。虽然承认获得相关组织的挑战，但这些发现为进一步的肠病相关环境因素生物标志物验证研究奠定了基础。
