A cross-sectional study of associations between the C-sucrose breath test, the lactulose rhamnose assay, and growth in children at high risk of environmental enteropathy.

Margaret N Kosek, Sarita Devi, Nirupama Shivakumar, Roger Yazbeck, Sayeeda Huq, Victor O Owino, Douglas J Morrison, Paul Kelly, Maribel Paredes-Olortegui, Silvenus Ochieng Konyole, Andrew F Brouwer, Gwenyth O Lee

Journal: The American journal of clinical nutrition 2024;120(6):1354-1363

PMID: 39384142

Abstract

BACKGROUND

Environmental enteropathy' (EE) is common among children who are highly exposed to enteric pathogens in low-resource settings. We optimized and validated a stable isotope-based breath test of intestinal sucrase activity (C-SBT) as a noninvasive test of carbohydrate digestion and metabolism.

OBJECTIVES

The primary objective of this study was to assess the relationship between the C-SBT and the lactulose/rhamnose ratio (LR) and growth in children. Secondary objectives were to assess the relationship between the C-SBT and additional biomarkers of EE. We also characterized the relationship between the C-SBT and child sex and dietary diversity, as well as household socio-economic status and food security.

METHODS

In this cross-sectional study, 12-to-15-mo-old children were recruited in Bangladesh, India, Kenya, and Peru. Children were assessed with a 4-h C-SBT and a 90-min LR test. Plasma was collected to determine the citrulline and kynurenine/tryptophan ratio. Length and weight were measured, and other variables were assessed through questionnaires. For a subset of children, anthropometry was re-measured after 3 mo. Linear regression was used to examine associations corresponding to each objective.

RESULTS

Three sites generated C-SBT breath curves that enabled pooled analysis. Differences in C-SBT breath curves, LR ratios, and other EE biomarkers were observed between sites. No associations were observed for C-SBT summary measures and LR or child growth [e.g., the association between LR and cumulative percent dose recovered at 90 min: -0.39; 95% confidence interval (CI): -1.79, 0.70]. Length-for-age and weight-for-age were positively associated with the time to 50% of dose recovered (0.05; 95% CI: 0.01, 0.09, and 0.05; 95% CI: 0.02, 0.07, respectively), and dietary diversity was associated with time at which 50% of the dose recovered by 240 min is recovered and cumulative percent dose recovered at 90 min (-0.10; 95% CI: -0.18, -0.02 and 2.67; 95% CI: 0.47, 4.88, respectively).

CONCLUSIONS

In children at risk of EE, there were no associations between the C-SBT, LR, or other EE biomarkers encompassing different pathophysiological domains of EE. This trial was registered at clinicaltrials.gov as NCT04109352.

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Address: Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences (a Unit of CBCI Society for Medical Education), Bangalore, India.; International Centre for Diarrhoeal Disease Research, Bangladesh.; Investigaciones Biomédicas, Asociación Benéfica PRISMA, Iquitos, Perú.; Department of Nutritional Sciences, Masinde Muliro University of Science and Technology, Kakamega, Kenya.; Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, South Australia, Australia.; Division of Human Health, Nutritional and Health-Related Environmental Studies Section, International Atomic Energy Agency, Vienna, Austria.; Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States.; Investigaciones Biomédicas, Asociación Benéfica PRISMA, Iquitos, Perú; Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, United States.; Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia; Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.; Scottish Universities Environmental Research Centre (SUERC), University of Glasgow, Scotland, United Kingdom.; Rutgers Global Health Institute, Department of Biostatistics and Epidemiology, School of Public Health, Rutgers, the State University of New Jersey, New Brunswick, NJ, United States. Electronic address: [email protected].
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