Environmental enteric dysfunction (EED) is a complex disorder characterised by structural and functional aberrations within the small intestine^{(Reference Crane, Jones and Berkley1)}. It is hypothesised that EED is the result of repeated enteric infections combined with under-nutrition and is prevalent throughout low and middle income countries. EED is thought to compromise linear growth potentially leading to stunting in infants^{(Reference Butler, Kosek and Krebs2)}. Stunting currently affects 144 million children globally under the age of 5⁽³⁾. ¹³C-sucrose from naturally enriched maize sources has previously been used in a breath test to assess intestinal sucrase activity as a marker of mucosal integrity and function in enteric enteropathy^{(Reference Ritchie, Brewster and Davidson4)}. However, this test requires up to 20 g of naturally ¹³C enriched sucrose to achieve acceptable signal-to-noise in breath ¹³CO₂, making the test unsuitable for routine use in infants. The current study aimed to develop a new ¹³C sucrose breath test (SBT) protocol using commercially available, highly enriched ¹³C Sucrose to facilitate a much smaller test dose.

This was a randomised crossover trial of 19 healthy adults recruited in Glasgow, UK. All participants completed a baseline SBT with 20 g naturally enriched sucrose before being randomly assigned to two groups; receiving 20 g unlabelled (beet) sucrose + 50 mg tracer (n = 8) or 50 mg tracer dose alone (n = 11). Participants remained allocated to their group and were given in a random repeated order ¹³C₁₂-Sucrose, ¹³C₆ Sucrose (¹³C₆-Fructose) and ¹³C₆ Sucrose (¹³C₆-Glucose) to assess the effect of labelling position on breath recovery parameters with at least 3 days washout between tests.

Results were expressed as Area Under the Curve (AUC), time of maximum breath ¹³CO₂ enrichment (T_max, hrs), cumulative percentage dose recovered at 90 mins (cPDR90, %) and time at which 50% AUC had been expired in breath 13CO2 (T_1/2, hrs).

Highly enriched ¹³C₁₂ sucrose yielded significantly improved ¹³C breath signal to noise compared to the naturally enriched sucrose dose (x20). There were no significant differences in AUC, cPDR90, T_max or T_1/2 between ¹³C₁₂ sucrose and naturally enriched sucrose (all P > 0.05). Altering the position of the ¹³C label changed kinetics of breath ¹³C excretion. ¹³CO₂ appeared more rapidly with ¹³C₆ sucrose (¹³C₆-fructose) compared with ¹³C₆ sucrose (¹³C₆-glucose) (T_max,(SD) = 1.29 (0.44) vs. 1.87 (0.22), P < 0.05 and cPDR90 (SD) = 15.95 (3.88) vs. 12.38 (2.31), P < 0.05 respectively). Addition of 20 g unlabelled sucrose appeared to slow down ¹³C sucrose digestion with significantly lower cPDR90 for all highly enriched variants (all P < 0.05).

A dose of 50 mg ¹³C₁₂-sucrose gave excellent signal-to-noise in breath ¹³CO₂ and there was no statistically significant difference in breath parameters compared with the naturally enriched SBT. The ¹³C labelling pattern impacted the kinetics of ¹³C recovery in breath probably reflecting intermediary metabolism. A minimal dose of ¹³C₁₂-sucrose is likely to be suitable for studies in infants and children.