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 - 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.
