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New CRP: The Efficacy of Amino Acid Supplementation in Treating Environmental Enteric Dysfunction Among Children at Risk of Malnutrition (E43036)

New Coordinated Research Project

This new coordinated research project (CRP) seeks to merge lessons and results from two on-going IAEA CRPs to provide information on the intersection between environmental enteric dysfunction (EED) and protein metabolism. The first CRP (E41016), involves the optimization and testing of the applicability of a novel stable isotope method to diagnose EED in children based on sucrose breath test in six low-and-middle-income countries (LMICs) with technical support from Australia and UK. Under the second CRP (E43031), a stable isotope method to measure protein quality from plant-based diets based on oro-ileal amino acid digestibility has been developed and applied in seven LMICs with technical support from France and UK. The dual tracer isotope technique, in which an intrinsically isotope-labeled test protein is simultaneously fed with a different isotope-labeled ‘reference’ protein, whose digestibility is known, enables assessment of true protein digestion.

EED is caused by subclinical infection due to enteric pathogens that thrive in conditions of poor sanitation and hygiene. It is characterized by villous atrophy, crypt hyperplasia, increased intestinal permeability, inflammatory cell infiltrate, and possibly nutrient malabsorption. The increased gut permeability, often measured by oral lactulose and mannitol test, is related to gut barrier dysfunction, with translocation of pathogenic organisms and endotoxins. EED is known to be an important component of the causal origin of undernutrition and stunting in infants in LMICs as it reduces the efficacy of nutritional interventions. Protein supply is a major contributor to support normal growth, yet very little is known on the impact of EED on protein digestion and amino acid absorption. The objective of this CRP is to use a combination of nuclear techniques to assess the response of EED to a short course of targeted amino acid supplementation. The CRP will provide the evidence base to enable Member States to formulate policies to improve optimal child growth and development. Further, the CRP results would contribute to the revision of the global clinical management and feeding regimens for stunted children complicated with or without EED, for the promotion of linear growth and the reduction in morbidity and mortality of vulnerable children in LMICs.

Nuclear component

A combination of two non-invasive stable isotope techniques, namely a dual tracer (deuterium and 13-carbon) method for assessment of protein digestion and a stable isotope based (13-carbon sucrose) breath test to assess nutrient absorption as an indicator of intestinal function will be applied in the new CRP. The dual tracer stable isotope technique enables a quick, non-invasive and accurate assessment of the digestion and absorption of protein from the diet. A test food is labelled with an isotope (typically deuterium or 13C) at the point of food preparation or during production in the field. For example, to determine amino acid absorption from a plant, deuterium is added to irrigation water during growth. Subsequently, a test meal is prepared from the labelled edible portion of the test food, which is then consumed by the study participant along with another isotope (carbon-13)-labelled highly digestible protein source. Blood samples are collected before the test meal is consumed and again five, six, seven and eight hours after the test meal and the blood amino acid concentration is analysed. The appearance of labelled amino acids in the blood relative to the test meal are used to calculate the digestibility of the legume protein. The 13C Sucrose Breath Test (13C-SBT) is based on the simple principle that, in the intestine, sucrose is broken down by a brush border enzyme called sucrase-isomaltase into glucose and fructose. When these are oxidized for use by the body, carbon-13 dioxide (13CO2) and water are produced. In abnormal circumstances, as in EED, sucrase enzyme activity and therefore 13CO2 production may be reduced or delayed.

CRP Overall Objective

To use a combination of existing nuclear techniques to assess the response of EED to a short course of targeted amino acid supplementation among children.

Specific Research Objectives

  1. To develop and test the applicability of a combined minimally invasive protocol for the dual stable isotope tracer method for protein digestion (DSIT) and the 13-C Sucrose Breath Test (13-C SBT) to assess nutrient absorption in the context of EED.
  2. To assess the interaction between EED and protein metabolism
  3. To assess the efficacy of amino acid supplementation on the treatment of EED in children.

Expected outcome

New information on the efficacy of interventions to treat EED generated and used as the basis to provide guidance on the design and implementation of programmes to reduce stunting in LMICs.

How to join this CRP

Please submit your Proposal for Research Contract or Agreement by email, no later than 15 January, 2021 to the IAEA’s Research Contracts Administration Section, using the appropriate template on the CRA web portal. Note that the same template can be used for both research contract and technical contract.

For further information related to this CRP, potential applicants should use the contract form under the CRP page.

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