13C-sucrose breath test for the non-invasive assessment of environmental enteropathy in Zambian adults

Abstract

Objectives Environmental enteropathy (EE) is a subclinical disorder highly prevalent in tropical and disadvantaged populations and is thought to play a role in growth faltering in children, poor responses to oral vaccines, and micronutrient deficiencies. This study aims to evaluate the potential of a non-invasive breath test based on stable isotopes for evaluation of impaired digestion and absorption of sucrose in EE. Methods We optimized a 13 C-sucrose breath test ( 13 C-SBT) in 19 young adults in Glasgow, United Kingdom. In a further experiment (in 18 adults) we validated the 13 C-SBT using Reducose, an intestinal glucosidase inhibitor. We then compared the 13 C-SBT to intestinal mucosal morphometry, immunostaining for sucrose-isomaltase (SI) expression, and SI activity in 24 Zambian adults with EE. Results Fully labeled sucrose (0.3 mg/kg) provided clear breath enrichment signals over 2–3 h in both British and Zambian adults, more than fivefold higher than naturally enriched sucrose. Reducose dramatically impaired 13 C-sucrose digestion, reducing 4 h 13 CO 2 breath recovery by > 50%. Duodenal biopsies in Zambian adults confirmed the presence of EE, and SI immunostaining was present in 16/24 adults. The kinetics of 13 CO 2 evolution were consistently faster in participants with detectable SI immunostaining. Although sucrase activity was strongly correlated with villus height ( r = 0.72; P < 0.05) after adjustment for age, sex and body mass index, there were no correlations between 13 C-SBT and villus height or measured sucrase activity in pinch biopsies. Conclusion A 13 C-SBT was developed which was easy to perform, generated clear enrichment of 13 CO 2 in breath samples, and clearly reports sucrase activity. Further work is needed to validate it and understand its applications in evaluating EE.