环境肠道功能障碍的生物标志物与塞拉利昂中度急性营养不良儿童的恢复和生长情况相关。
Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone.
机构信息
Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA.
出版信息
Am J Clin Nutr. 2021 Jun 1;113(6):1556-1564. doi: 10.1093/ajcn/nqaa434.
BACKGROUND
Environmental enteric dysfunction (EED) may influence growth during and recovery from moderate acute malnutrition (MAM), however, biomarkers to assess these relations have yet to be identified.
OBJECTIVES
The objectives of this study were to: 1) develop a score for EED based on host fecal mRNA transcripts, 2) compare biomarkers of EED with each other, and 3) examine associations between the EED biomarkers and recovery from MAM and growth outcomes.
METHODS
In a cohort of 520 Sierra Leonean MAM children, biomarkers of EED included the lactulose: mannitol (L: M) test, 15 host fecal mRNA transcripts, and host fecal proteins [α-1-antitrypsin (AAT), myeloperoxidase (MPO), neopterin (NEO)]. Anthropometry data were also collected and z scores were computed for length-for-age (LAZ) and weight-for-length (WLZ). Recovery from MAM was defined as midupper arm circumference ≥12.5 cm. Factor analysis was used to identify EED scores using the mRNA transcripts, and mixed effects regression was conducted to test for associations.
RESULTS
The 15 host fecal mRNA transcripts were clustered into 3 scores: gut inflammation (GI) score, gut structure (GS) score, and gut defense (GD) score. We found agreement between certain inflammation markers (GI score and MPO), and permeability markers (GS score and AAT; AAT and the L: M excretion ratio). Antimicrobial gut defense (GD score) was inversely associated with percent lactulose excreted, a measure of intestinal permeability. LAZ (β: -0.08; 95% CI: -0.14, -0.02) and WLZ (β: -0.03; 95% CI: -0.06, -0.01) were negatively associated with GI score. A high GD score (β: 0.36; 95% CI: 0.08, 0.64) and low AAT (β: -1.35; 95% CI: -2.35, -0.36) were associated with recovery from MAM.
CONCLUSIONS
Scores derived from host fecal mRNA transcript variably correlated with the L: M test and host fecal proteins. Markers of intestinal inflammation, permeability, and defense were associated with growth outcomes and recovery from MAM.
背景
环境肠道功能障碍（EED）可能会影响中度急性营养不良（MAM）期间和恢复期的生长，但评估这些关系的生物标志物尚未确定。
目的
本研究的目的是：1）基于宿主粪便 mRNA 转录本建立 EED 评分，2）比较 EED 生物标志物之间的关系，3）探讨 EED 生物标志物与 MAM 恢复和生长结果之间的关系。
方法
在 520 名塞拉利昂 MAM 儿童队列中，EED 的生物标志物包括乳果糖：甘露醇（L：M）试验、15 种宿主粪便 mRNA 转录本和宿主粪便蛋白[α-1-抗胰蛋白酶（AAT）、髓过氧化物酶（MPO）、新蝶呤（NEO）]。还收集了人体测量学数据，并计算了年龄别身长（LAZ）和身长别体重（WLZ）的 Z 分数。MAM 恢复的定义为中上臂围≥12.5cm。使用 mRNA 转录本进行因子分析以确定 EED 评分，并进行混合效应回归以检验相关性。
结果
15 种宿主粪便 mRNA 转录本聚集成 3 个评分：肠道炎症（GI）评分、肠道结构（GS）评分和肠道防御（GD）评分。我们发现某些炎症标志物（GI 评分和 MPO）和通透性标志物（GS 评分和 AAT；AAT 和 L：M 排泄率）之间存在一致性。抗菌肠道防御（GD 评分）与肠道通透性的衡量指标——乳果糖排泄百分比呈负相关。LAZ（β：-0.08；95%CI：-0.14，-0.02）和 WLZ（β：-0.03；95%CI：-0.06，-0.01）与 GI 评分呈负相关。高 GD 评分（β：0.36；95%CI：0.08，0.64）和低 AAT（β：-1.35；95%CI：-2.35，-0.36）与 MAM 恢复相关。
结论
源自宿主粪便 mRNA 转录本的评分与 L：M 试验和宿主粪便蛋白呈不同程度的相关性。肠道炎症、通透性和防御标志物与生长结果和 MAM 恢复相关。
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