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

Robert J Schillinger; Simutanyi Mwakamui; Chola Mulenga; Mizinga Tembo; Phoebe Hodges; Ellen Besa; Kanta Chandwe; Victor O Owino; Christine A Edwards; Paul Kelly; Douglas J Morrison

doi:10.3389/fmed.2022.904339

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

Front Med (Lausanne). 2022 Jul 29:9:904339. doi: 10.3389/fmed.2022.904339. eCollection 2022.

Authors

Robert J Schillinger^{1

2}, Simutanyi Mwakamui³, Chola Mulenga³, Mizinga Tembo³, Phoebe Hodges^{3

4}, Ellen Besa³, Kanta Chandwe³, Victor O Owino⁵, Christine A Edwards², Paul Kelly^{3

4}, Douglas J Morrison¹

Affiliations

¹ Scottish Universities Environmental Research Centre, University of Glasgow, East Kilbride, United Kingdom.
² School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, United Kingdom.
³ Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.
⁴ Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, United Kingdom.
⁵ Nutritional and Health-Related Environmental Studies Section, Division of Human Health, International Atomic Energy Agency (IAEA), Vienna, Austria.

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 ¹³C-sucrose breath test (¹³C-SBT) in 19 young adults in Glasgow, United Kingdom. In a further experiment (in 18 adults) we validated the ¹³C-SBT using Reducose, an intestinal glucosidase inhibitor. We then compared the ¹³C-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 ¹³C-sucrose digestion, reducing 4 h ¹³CO₂ 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 ¹³CO₂ 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 ¹³C-SBT and villus height or measured sucrase activity in pinch biopsies.

Conclusion: A ¹³C-SBT was developed which was easy to perform, generated clear enrichment of ¹³CO₂ in breath samples, and clearly reports sucrase activity. Further work is needed to validate it and understand its applications in evaluating EE.

Keywords: 13C-breath test; environmental enteropathy; gut function; intestinal sucrase activity; malnutrition; stunting.