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

项目总结 环境肠道功能障碍(EED)是一种获得性的小肠亚临床疾病，目前 被认为是儿童期线性发育迟缓及其相关的终生健康差距的主要原因 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， 增加对微生物的通透性，导致粘膜和全身炎症。一旦在以下条件下获得 婴儿期的不卫生条件和病原体暴露，EED通常会持续到成年， 全球的病例数量被认为是数亿例。尽管假定会产生终生影响，但 对生长发育影响的研究从来没有超过5岁的系统研究。此外， 能量消耗的EED-被认为是儿童发育迟缓的核心原因-从来没有 在任何年龄段都被研究过。这些知识上的差距在一定程度上与传统入侵的负担有关 评定电火工品的抽样方法。拟议的研究有三个具体目标：第一，优化 微创指刺干血中主要EED生物标志物检测方法的初步验证 现场样品。第二，确定EED对学龄儿童纵向生长的影响。 第三，定义儿童期EED和测量的能量消耗之间的关系。我们很好- 我们有能力承担这项工作，因为我们可以利用独特的现有数据和生物样品集 来自厄瓜多尔亚马孙的土著Shuar人的320名学龄儿童(4-12岁)。 人类营养中的主要能量模型是相加的，这意味着习惯性地将卡路里消耗在任何 单一代谢任务(例如，免疫活动)相应地增加总能量消耗(TEE)和 每日总能源需求量。在EED的情况下，这个模型表明慢性炎症应该 增加TEE，导致增长因随后的能源短缺而步履蹒跚。挑战这种模式，我们有 显示炎症和其他形式的免疫活动对舒阿尔儿童的TEE没有影响 事实上，生活在农村和城市的儿童每天消耗的卡路里总量是相同的。 这些发现表明，儿童习惯性发球台是相对稳定的，而不是相加的。 跨越不同的环境。EED背景下的受限TEE可以解释由于以下原因导致的增长停滞 能量分配与慢性炎症的权衡，而不考虑能量的可用性，这是一个预测 来自营养补充剂研究的数据表明，增长的改善微乎其微。在这里，我们 将推动我们在Shuar中的工作，以包括EED的关键措施。预计结果将进一步 挑战儿童能量消耗的相加模型，提高对儿童精神分裂症病因的认识 增长步履蹒跚，能源平衡，终身健康和人力资本差距。作为R15区域，这 该项目将改善贝勒大学的本科生生物医学研究环境，并将支持实践 每年至少有四名本科生在PI的实验室进行培训和研究。

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.