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Application of Stable Isotope Techniques in Environmental Enteric Dysfunction Assessment and Understanding its Impact on Child Growth
Closed for proposals
Project Type
Project Code
E41016CRP
2136Approved Date
Status
Start Date
Expected End Date
Completed Date
23 March 2023Participating Countries
Description
Retarded linear growth, widely referred to as stunting, is rampant in low and middle income countries, affecting a total of 161 million 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 aims to validate and apply a novel, non-invasive stable isotope technique (13C Sucrose Breath Test) to foster a better understanding of pathways underpinning EED and child growth. The key results of the CRP will be: 1) non-invasive 13C Sucrose Breath Test to diagnose EED and assess its effects on health; 2) improved technical capacity to diagnose and assess health of EED populations; 3) new data on the pathways underpinning the relationship between EED and child growth including dietary, mucosal integrity/permeability and nutrient and energy partitioning. The ultimate outcome will be a better understanding of the relationship between EED and child growth which will in turn contribute to the development of diagnostic tools for EED to facilitate its prevention, treatment and management to ensure good health.
Objectives
To validate and apply a novel, non-invasive stable isotope technique (13C Sucrose Breath Test) to foster a better understanding of pathways underpinning EED and child growth.
Impact
The main strength of the CRP was the unified and harmonised protocol used across countries. This led to comparable results with greater global public health impact than might have been achieved from smaller country-specific studies run independently of one another. This CRP has inspired new TC Projects and new CRPs in addition to elevating IAEA visibility via a joint webinar with the European Association for Gastroenterology Endoscopy and Nutrition (EAGEN) and 7 publications in peer reviewed journals. More publications are at various stages of preparation. The main paper with results on assessment of EED in children was published in the American Journal of Clinical Nutrition, the most reputable and highly impactful journal in the nutrition field. The 13C-SBT was also published in the NTR 2024, further highlighting IAEA's work among its MS.
Relevance
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.