Mechanisms linking metabolism of Helicobacter pylori to (18)O and (13)C-isotopes of human breath CO(2)

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.