Application of Stable Isotope Techniques in Environmental Enteric Dysfunction Assessment and Understanding its Impact on Child Growth

Retarded linear growth, widely referred to as stunting, remains rampant in low- and middle-income countries, affecting millions of children under the age of five years; it develops in the first 1000 days of life, and becomes irreversible if no appropriate interventions are in place. Environmental Enteric Dysfunction (EED) is the presence of diffuse, upper small bowel villous atrophy accompanied by the presence of morphologic evidence of barrier disruption and inflammation. EED affects presumably 50-95% of all children under the age of 5 years in resource poor settings. Retarded growth, altered gut microbiota, and decreased vaccine responsiveness are considered the most important consequences of EED and are attributable to: altered intestinal structure and function, defects in nutrient absorption, reduced growth hormone activity, altered host immunity and change in microbiota composition and diversity. Despite the significance of EED to infant and child nutrition and health, biomarkers and simple diagnostic techniques for the definition and classification of EED are lacking. This CRP has aided a better understanding of the relationship between EED and child growth.

A publication in the American Journal of Clinical Nutrition, the most reputable and high impact journal in the nutrition field, presented results from the main study in Bangladesh, Peru and India to test the applicability of a novel 13-carbon breath test (13C-SBT) to diagnose and classify EED. Increased leakiness and permeability, shortened intestinal villa, inflammation and bacterial translocation are the hallmarks of EED that can be measured using various techniques. In the 13C-SBT, an oral dose of a 13C-labeled sucrose tracer was digested, absorbed, and metabolized, appearing on the breath as 13CO2. Cumulative recovery of 13CO2 by a given time point was the standard summary measure of the 13C-SBT test. In the CRP, 13C-SBT was administered in children aged 12-15 months and was compared to endoscopy that measures intestinal villa height and to a dual sugar test that indicates permeability. Results showed that the 13C-SBT relates to neither intestinal structure nor permeability. Rather, 13C-SBT is applicable in understanding the breakdown of sucrose into fructose and glucose by the sucrase-isomaltose enzyme in the intestinal brush border; this represents nutrient absorption, one of EED domains. The test could potentially also be applied to explore sucrase activity in other related conditions that affect nutrient digestion such as severe acute malnutrition that affect pancreatic or liver function.