Oxygen-18 stable isotope of exhaled breath CO₂ as a non-invasive marker of Helicobacter pylori infection

We report for the first time the time-dependent excretion kinetics of ¹⁸O/¹⁶O isotope ratios of CO₂ in exhaled breath samples using an optical cavity-enhanced integrated cavity output spectroscopy (ICOS) method for the detection of Helicobacter pylori (H. pylori) infection in human stomach. We observed large differences in the oxygen-18 isotopic fractionations of breath CO₂ between H. pylori positive and negative individuals in response to orally administered, both unlabelled and labelled ¹³C-enriched urea, suggesting a potential link between H. pylori infections and the ¹⁸O-isotopic exchange in exhaled breath. An optimal diagnostic cut-off point of ¹⁸O/¹⁶O isotope ratios of breath CO₂ for the presence of H. pylori infection was determined to be 1.92‰ using the receiver operating characteristic curve (ROC) analysis, which exhibited both diagnostic sensitivity and specificity of 100% with an accuracy of 100%. Moreover, the methodology of monitoring ¹⁸O in breath CO₂ manifested both positive and negative predictive values of 100%, demonstrating excellent diagnostic accuracy and suggesting that breath C¹⁸O¹⁶O could be used as a potential marker for the identification of H. pylori infections. Our findings also suggest that monitoring the ¹⁸O/¹⁶O isotope ratios of breath CO₂ is a valid and sufficiently robust novel non-invasive approach for the accurate and specific detection of H. pylori infection in real-time, which may open new perspectives in the molecular diagnosis of H. pylori infection for large-scale screening purposes, early detection and follow-up of patients.