A model-based 13C-sucrose breath test diagnostic for gut function disorders characterized by a loss of sucrase-isomaltase enzymatic activity

Brouwer, A. F., Lee, G. O., Van Wyk, H., Schillinger, R. J., Edwards, C. A. and Morrison, D. J. (2024) A model-based 13C-sucrose breath test diagnostic for gut function disorders characterized by a loss of sucrase-isomaltase enzymatic activity. Journal of Nutrition, (doi: 10.1016/j.tjnut.2023.11.017) (PMID:37995914) (Early Online Publication)

Abstract

Background: Environmental enteric dysfunction (EED) causes malnutrition in children in low-resource settings. Stable-isotope breath tests have been proposed as noninvasive tests of altered nutrient metabolism and absorption in EED, but uncertainty over interpreting the breath curves has limited their use. The activity of sucrose-isomaltase, the glucosidase enzyme responsible for sucrose hydrolysis, may be reduced in EED. We previously developed a mechanistic model describing the dynamics of the 13C-sucrose breath test (13C-SBT) as a function of underlying metabolic processes. Objectives: This study aimed to determine which breath test curve dynamics are associated with sucrose hydrolysis and with the transport and metabolism of the fructose and glucose moieties and to propose and evaluate a model-based diagnostic for the loss of activity of sucrase-isomaltase. Methods: We applied the mechanistic model to 2 sets of exploratory 13C-SBT experiments in healthy adult participants. First, 19 participants received differently labeled sucrose tracers (U-13C fructose, U-13C glucose, and U-13C sucrose) in a crossover study. Second, 16 participants received a sucrose tracer accompanied by 0, 100, and 750 mg of Reducose, a sucrase-isomaltase inhibitor. We evaluated a model-based diagnostic distinguishing between inhibitor concentrations using receiver operator curves, comparing with conventional statistics. Results: Sucrose hydrolysis and the transport and metabolism of the fructose and glucose moieties were reflected in the same mechanistic process. The model distinguishes these processes from the fraction of tracer exhaled and an exponential metabolic process. The model-based diagnostic performed as well as the conventional summary statistics in distinguishing between no and low inhibition [area under the curve (AUC): 0.77 vs. 0.66–0.79] and for low vs. high inhibition (AUC 0.92 vs. 0.91–0.99). Conclusions: Current summary approaches to interpreting 13C breath test curves may be limited to identifying only gross gut dysfunction. A mechanistic model-based approach improved interpretation of breath test curves characterizing sucrose metabolism.

• Item Type: Articles
• Additional Information: This project was funded through the International Atomic Energy Agency (IAEA) coordinated research projects E4.10.16 and E430336, United States National Science Foundation (NSF) grant DMS1853032, and United States National Institutes of Health (NIH) grant K01AI145080.
• Keywords: environmental enteric dysfunction, breath test, 13C, stable isotope, mechanistic model, sucrose, fructose, glucose, Reducose, mulberry leaf extract.
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Edwards, Professor Christine and Schillinger, Robert and Morrison, Professor Douglas
• Authors: Brouwer, A. F., Lee, G. O., Van Wyk, H., Schillinger, R. J., Edwards, C. A., and Morrison, D. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing; College of Science and Engineering > Scottish Universities Environmental Research Centre
• Journal Name: Journal of Nutrition
• Publisher: Elsevier
• ISSN: 0022-3166
• ISSN (Online): 1541-6100
• Published Online: 21 November 2023