A cross-sectional study of associations between the ¹³C-sucrose breath test, the lactulose rhamnose assay, and growth in children at high risk of environmental enteropathy

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 (¹³C-SBT) as a noninvasive test of carbohydrate digestion and metabolism.

Objectives: The primary objective of this study was to assess the relationship between the ¹³C-SBT and the lactulose/rhamnose ratio (LR) and growth in children. Secondary objectives were to assess the relationship between the ¹³C-SBT and additional biomarkers of EE. We also characterized the relationship between the ¹³C-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 ¹³C-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 ¹³C-SBT breath curves that enabled pooled analysis. Differences in ¹³C-SBT breath curves, LR ratios, and other EE biomarkers were observed between sites. No associations were observed for ¹³C-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 ¹³C-SBT, LR, or other EE biomarkers encompassing different pathophysiological domains of EE. This trial was registered at clinicaltrials.gov as NCT04109352.