American journal of physiology. Endocrinology and metabolismAug 20, 2026

A noninvasive breath test to track delayed digestion caused by semaglutide treatment in mice

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 21, 2026

Abstract

A non-invasive breath test using 13C-labeled mannitol measures oral-cecal transit time in mice.

The test detects metabolism of mannitol by cecal microbiota, indicated by measurable 13CO2 in breath.
Indirect calorimetry and real-time analysis of the 13C/12C ratio enhance measurement accuracy.
This method allows for high-throughput, longitudinal studies in unrestrained, freely moving mice.
It addresses limitations of current OCTT measurement techniques, which are often invasive or stressful.
The approach may improve experimental rigor and reproducibility in gastrointestinal physiology research.

Simplified

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, are highly effective treatments for obesity and type 2 diabetes but are often associated with gastrointestinal side effects including delayed transit times through the gastrointestinal tract. We present a non-invasive breath test to measure oral-cecal transit time (OCTT) in mice that could be readily translated to clinical studies. Current methods for measuring OCTT are limited by invasiveness, terminal procedures, anesthesia, radioactive tracers, or stress-induced influence on the outcomes. Here we demonstrate that ¹³C-labeled mannitol is metabolized by murine cecal microbiota, producing measurable ¹³CO₂ in exhaled breath. Using indirect calorimetry combined with real-time measurement of the ¹³C/¹²C ratio, this approach provides a highly granular, non-invasive method to measure OCTT in mice. This technique is performed in unrestrained freely moving animals while enabling high-throughput measurements performed longitudinally. The method improves experimental rigor and reproducibility and provides a valuable tool for studying gastrointestinal physiology and the effects of pharmacologic therapies.

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A noninvasive breath test to track delayed digestion caused by semaglutide treatment in mice

Abstract

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