The impact of environmental enteric dysfunction on the growth and energy expenditure of school-age children: analysis of unique longitudinal data and finger-prick dried blood spot biomarkers

项目摘要 环境性肠功能障碍（EED）是一种获得性小肠亚临床状况， 被认为是儿童线性生长停滞及其相关的健康终身差异的主要原因 和人力资本。EED是一种复杂的疾病，其主要特征是肠道吸收能力差， 增加对微生物的渗透性，并导致粘膜和全身炎症。一旦获得， 不卫生的条件和病原体暴露在婴儿期，EED通常持续到成年， 据认为，全球病例数为数亿例。尽管假定存在寿命效应， EED对生长的影响从未被系统地研究过超过5岁。此外， EED对能量消耗的影响-被认为是儿童生长迟缓的病因学核心-从未 被研究，在任何年龄。这些知识上的差距部分与传统侵入性疾病的负担有关。 评估EED的抽样方法。该研究有三个具体目标：第一，优化 用于测量微创指刺干血中关键EED生物标志物的初步验证测定法 现场取样。第二，确定EED对学龄儿童纵向生长的影响。 第三，确定儿童EED和测量的能量消耗之间的关系。我们很好- 因为我们可以利用现有的独特数据和生物样本集， 320名学龄儿童（4-12岁）的土著Shuar人的亚马逊厄瓜多尔。 在人类营养中占主导地位的能量模型是加性的，这意味着习惯性地花费在任何食物上的卡路里 单一代谢任务（例如，免疫活性）相应地增加总能量消耗（TEE）， 日常能量需求。在EED的情况下，该模型表明慢性炎症应该 增加TEE，由于随后的能量不足导致生长停滞。根据这个模型，我们有 表明炎症和其他形式的免疫活动对Shuar儿童的TEE没有影响， 事实上，生活在农村和城市环境中的儿童每天消耗的卡路里总量相同。 这些发现表明，儿童的习惯性TEE相对稳定（即，“约束”） 在不同的环境中。在EED的背景下，受约束的TEE可以解释由于以下原因导致的生长停滞： 无论能量可用性如何，慢性炎症的能量分配权衡， 营养补充研究的数据支持这一点，这些数据显示，生长方面的改善微不足道。这里我们 将推进我们在Shuar的工作，包括EED的关键措施。预计结果将进一步 挑战儿童能量消耗的加法模型，提高对 增长停滞、能源平衡以及终生健康和人力资本差距。作为一个R15区域， 该项目将加强贝勒大学本科生生物医学研究环境，并将支持动手 每年至少有四名本科生在PI实验室接受培训和研究。

PROJECT SUMMARY Environmental enteric dysfunction (EED), an acquired subclinical condition of the small intestine, is now viewed as a leading cause of childhood linear growth faltering and its associated lifetime disparities in health and human capital. A complex condition, EED is characterized primarily by poor intestinal absorptive capacity, increased permeability to microbes, and resulting mucosal and systemic inflammation. Once acquired under unsanitary conditions and pathogen exposure during infancy, EED typically persists into adulthood, and the number of cases globally is thought to be hundreds of millions. Despite presumed lifetime effects, the impact of EED on growth has never been systematically investigated beyond the age of 5 years. Moreover, the impact of EED on energy expenditure – thought to be central to the etiology of childhood growth faltering – has never been studied, at any age. These gaps in knowledge relate, in part, to the burden of traditional invasive sampling methods for assessing EED. The proposed study has three specific aims: First, to optimize preliminarily validated assays for measuring key EED biomarkers in minimally invasive finger-prick dried blood spot samples. Second, to determine the impact of EED on longitudinal growth among school-age children. Third, to define relationships between childhood EED and measured energy expenditure. We are well- positioned to undertake this work because we can capitalize on a unique existing data and biospecimen set from 320 school-age children (age 4-12 years) among the Indigenous Shuar people of Amazonian Ecuador. Predominant energetic models in human nutrition are additive, implying that calories habitually spent on any single metabolic task (e.g., immune activity) correspondingly increase total energy expenditure (TEE) and overall daily energy requirements. In the case of EED, this model suggests that chronic inflammation should increase TEE, resulting in growth faltering due to subsequent energy deficit. Challenging this model, we have shown that inflammation and other forms of immune activity have no impact on TEE among Shuar children and, in fact, that children living in rural and urban contexts spend the same total number of calories each day. These findings suggest that, rather than additive, children’s habitual TEE is relatively stable (i.e., “constrained”) across diverse environments. Constrained TEE in contexts of EED can explain growth faltering as the result of energy allocation trade-offs with chronic inflammation, irrespective of energy availability, a prediction that is supported by data from nutrition supplementation studies showing negligible improvements in growth. Here, we would advance our work among the Shuar to include key measures of EED. Results are expected to further challenge the additive model of children’s energy expenditure, improving understanding of the etiology of growth faltering, energy balance, and lifetime health and human capital disparities. As an R15 AREA, this project will enhance the undergraduate biomedical research environment at Baylor and will support hands-on training and research experience for a minimum of four undergraduate students each year in the PI’s lab.