Mechanisms linking metabolism of Helicobacter pylori to 18 O and 13 C-isotopes of human breath CO2

Abstract

The gastric pathogen Helicobacter pylori utilize glucose during metabolism, but the underlying mechanisms linking to oxygen-18 (18 O) and carbon-13 (13 C)-isotopic fractionations of breath CO 2 during glucose metabolism are poorly understood. Using the excretion dynamics of 18 O/ 16 O and 13 C/ 12 C-isotope ratios of breath CO 2, we found that individuals with Helicobacter pylori infections exhibited significantly higher isotopic enrichments of 18 O in breath CO 2 during the 2h-glucose metabolism regardless of the isotopic nature of the substrate, while no significant enrichments of 18 O in breath CO 2 were manifested in individuals without the infections. In contrast, the 13 C-isotopic enrichments of breath CO 2 were significantly higher in individuals with Helicobacter pylori compared to individuals without infections in response to 13 C-enriched glucose uptake, whereas a distinguishable change of breath 13 C/ 12 C-isotope ratios was also evident when Helicobacter pylori utilize natural glucose. Moreover, monitoring the 18 O and 13 C-isotopic exchange in breath CO 2 successfully diagnosed the eradications of Helicobacter pylori infections following a standard therapy. Our findings suggest that breath 12 C 18 O 16 O and 13 C 16 O 16 O can be used as potential molecular biomarkers to distinctively track the pathogenesis of Helicobacter pylori and also for eradication purposes and thus may open new perspectives into the pathogen's physiology along with isotope-specific non-invasive diagnosis of the infection.