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

Abstract

The gastric pathogen Helicobacter pylori utilize glucose during metabolism, but the underlying mechanisms linking to oxygen-18 (18O) and carbon-13 (13C)-isotopic fractionations of breath CO2 during glucose metabolism are poorly understood. Using the excretion dynamics of 18O/16O and 13C/12C-isotope ratios of breath CO2, we found that individuals with Helicobacter pylori infections exhibited significantly higher isotopic enrichments of 18O in breath CO2 during the 2h-glucose metabolism regardless of the isotopic nature of the substrate, while no significant enrichments of 18O in breath CO2 were manifested in individuals without the infections. In contrast, the 13C-isotopic enrichments of breath CO2 were significantly higher in individuals with Helicobacter pylori compared to individuals without infections in response to 13C-enriched glucose uptake, whereas a distinguishable change of breath 13C/12C-isotope ratios was also evident when Helicobacter pylori utilize natural glucose. Moreover, monitoring the 18O and 13C-isotopic exchange in breath CO2 successfully diagnosed the eradications of Helicobacter pylori infections following a standard therapy. Our findings suggest that breath 12C18O16O and 13C16O16O 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.

Simultaneous Sensitive Determination of δ13C, δ18O, and δ17O in Human Breath CO2 Based on ICL Direct Absorption Spectroscopy

“…In addition, a growing body of evidence suggests that the effects of H. pylori may also be relevant to several other extragastric diseases including idiopathic thrombocytopenic purpura, cardiovascular disease, anemia, diabetes, and insulin resistance [11,12]. In recent years, a few studies have reported that the oxygen-18 ( 18 O) isotopes in exhaled CO 2 are also a biomarker related to H. pylori because of the rapid exchange of the 16 O in 12 C 16 O 2 and 18 O in H 2 18 O in response to periplasmic α-carbonic anhydrase activity [13][14][15].…”

“…For gas identification and quantification, there are significant advantages to laser absorption spectroscopy, such as high sensitivity, high selectivity, fast response, and realtime online analysis [16][17][18][19][20]. Many laser absorption spectroscopy based sensors have been developed for monitoring the human breath CO 2 isotopes in recent years, especially for 13 C. Generally, the δ value has been used to describe the relative deviation of the sample isotope ratio from the standard reference value (e.g., the standard abundance in Vienna Peedee Belemnite (VPDB)). Crosson et al constructed a cavity ring-down spectrometer using a three-mirror high-finesse ring-down cavity, and demonstrated the ability to obtain δ 13 C in breath samples [21].…”

“…Many laser absorption spectroscopy based sensors have been developed for monitoring the human breath CO 2 isotopes in recent years, especially for 13 C. Generally, the δ value has been used to describe the relative deviation of the sample isotope ratio from the standard reference value (e.g., the standard abundance in Vienna Peedee Belemnite (VPDB)). Crosson et al constructed a cavity ring-down spectrometer using a three-mirror high-finesse ring-down cavity, and demonstrated the ability to obtain δ 13 C in breath samples [21]. Kasyutich et al developed an off-axis cavity-enhanced absorption spectrometer, and estimated δ 13 C standard deviations of 1.8‰ and 3.7‰ based on peak height and integrated area estimations, respectively [22].…”

“…Kasyutich et al developed an off-axis cavity-enhanced absorption spectrometer, and estimated δ 13 C standard deviations of 1.8‰ and 3.7‰ based on peak height and integrated area estimations, respectively [22]. A multidimensional linear regression technique to calculate the δ 13 C isotope was reported by Andreev et al, and precision of 0.07‰ was obtained at an averaging time of 3 min thanks to a Herriott multipass cell [23]. Based on an off-axis integrated cavity output spectroscopy system, Pradhan's group studied the mechanisms linking exhaled δ 13 C and δ 18 O of CO 2 to H. pylori [12][13][14][15].…”

Real-Time Monitoring of 13C- and 18O-Isotopes of Human Breath CO2 Using a Mid-Infrared Hollow Waveguide Gas Sensor

“…By taking a small amount of 13 C-labeled pills, a suspected H. pylori patient will exhibit enrichment of 13 CO 2 in the exhaled gas, which is usually reported as the delta over baseline (DOB) value relative to a standard [3][4] . Recently, the 18 Oisotope of CO 2 in exhaled gas was also demonstrated as a potential molecular biomarker to track the pathogenesis of H. pylori 5 distinctively. A δ DOB 13 C ≥2.0‰ or δ DOB 18 O ≥1.92‰ is strongly relevant with the infection of H. pylori in the human stomach [6][7] .…”