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Over the past several decades, it has been generally believed that microbial nitrification and denitrification are not significant processes in the human gastrointestinal tract. Moreover, the underlying physiological link between exhaled nitrous oxide (N 2 O) and aerobic denitrification in the gastric environment is still largely unknown. In this report, we provide direct experimental evidence of the aerobic denitrification process in the human gastrointestinal tract by evaluating concentrations of dissolved N 2 O and its precursor nitrite ([Formula: see text]) ion in the gastric juice along with exhaled N 2 O concentration using a high-precision laser spectroscopy technique. Moreover, in vitro studies of gastric fluid in patients reveal a new mechanism of nitrification of ammonium ion ([Formula: see text]) followed by denitrification of [Formula: see text] leading to the formation of N 2 O in the gastric environment, which is eventually excreted in exhaled breath. This observation was subsequently validated under in vivo physiological conditions exploiting the urease activity of the gastric pathogen Helicobacter pylori. Consequently, our findings established a strong physiological link between exhaled N 2 O and bacterial infection in the stomach. This deepens our understanding of the unusual microbial denitrification in the gastric environment, providing new insight into the activities of human-associated microorganisms, which eventually affect the human physiology and health.

Helicobacter pylori causes several gastrointestinal diseases and may also contribute to the development of type 2 diabetes (T2D). Several studies suggest that there might be a potential link between H. pylori infection and T2D, but it still remains the subject of debate. Here, we first report the cumulative effect of H. pylori infection and T2D by exploiting the excretion kinetics of 13 C/ 12 C and 18 O/ 16 O isotope ratios of exhaled breath CO 2 in response to an oral dose of 13 C-enriched glucose in individuals with T2D and non-diabetic controls (NDC) harbouring the H. pylori infection. Using a high-resolution integrated cavity output spectroscopy (ICOS) technique in the infrared region, we observed that the isotopic fractionations of 13 C and 18 O in breath CO 2 are distinctly altered in H. pylori infected T2D patients as well as in H. pylori infected NDC. Several optimal diagnostic cut-off points of 13 C and 18 O isotopes of breath CO 2 were also determined which exhibited the diagnostic sensitivity and specificity of ∼97 % and thus suggesting that breath 13 C and 18 O isotopes might be considered as potential biomarkers for the non-invasive assessment of the gastric pathogen prior to the onset of T2D. This may open a new diagnostic strategy for treating these common diseases in an alternative way.

The gastric pathogen Helicobacter pylori utilizes molecular hydrogen (H2) as a respiratory substrate during colonization in the gastric mucosa. However, the link between molecular H2 and the pathogenesis of peptic-ulcer disease (PUD) and non-ulcerous dyspepsia (NUD) by the enzymatic activity of H. pylori still remains mostly unknown. Here we provide evidence that breath H2 excretion profiles are distinctly altered by the enzymatic activity of H. pylori for individuals with NUD and PUD. We subsequently unravelled the potential molecular mechanisms responsible for the alteration of H2 in exhaled breath in association with peptic ulcers, encompassing both gastric and duodenal ulcers, along with NUD. We also established that carbon-isotopic fractionations in the acid-mediated bacterial environment regulated by bacterial urease activity cannot discriminate the actual disease state i.e. whether it is peptic ulcer or NUD. However, our findings illuminate the unusual molecular H2 in breath that can track the precise evolution of PUD and NUD, even after the eradication of H. pylori infection. This deepens our understanding of the pathophysiology of PUD and NUD, reveals non-invasively the actual disease state in real-time and thus offers a novel and robust new-generation strategy for treating peptic-ulcer disease together with non-ulcer related complications even when the existing (13)C-urea breath test ((13)C-UBT) fails to diagnose.

There is a pressing need to develop a novel early-detection strategy for the precise evolution of small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome (IBS) patients. The current method based on a hydrogen breath test (HBT) for the detection of SIBO is highly controversial. HBT has many limitations and drawbacks. It often fails to indentify SIBO when IBS individuals have 'non-hydrogen-producing' colonic bacteria. Here, we show that hydrogen sulphide (H2S) in exhaled breath is distinctly altered for diarrhea-predominant IBS individuals with positive and negative SIBO by the activity of intestinal sulphate-reducing bacteria. Subsequently, by analyzing the excretion kinetics of breath H2S, we found a missing link between breath H2S and SIBO when HBT often fails to diagnose SIBO. Moreover, breath H2S can track the precise evolution of SIBO, even after the eradication of bacterial overgrowth. Our findings suggest that the changes in H2S in the bacterial environment may contribute to the pathogenesis of SIBO and the breath H2S as a potential biomarker for non-invasive, rapid and precise assessment of SIBO without the endoscopy-based microbial culture of jejunal aspirates, and thus may open new perspectives into the pathophysiology of SIBO in IBS subjects.

We report for the first time the excretion kinetics of the percentage dose of (13)C recovered/h ((13)C-PDR %/h) and cumulative PDR, i.e. c-PDR (%) to accomplish the highest diagnostic accuracy of the (13)C-urea breath test ((13)C-UBT) for the detection of Helicobacter pylori infection without any risk of diagnostic errors using an optical cavity-enhanced integrated cavity output spectroscopy (ICOS) method. An optimal diagnostic cut-off point for the presence of H. pylori infection was determined to be c-PDR (%) = 1.47 % at 60 min, using the receiver operating characteristic curve (ROC) analysis to overcome the "grey zone" containing false-positive and false-negative results of the (13)C-UBT. The present (13)C-UBT exhibited 100 % diagnostic sensitivity (true-positive rate) and 100 % specificity (true-negative rate) with an accuracy of 100 % compared with invasive endoscopy and biopsy tests. Our c-PDR (%) methodology also manifested both diagnostic positive and negative predictive values of 100 %, demonstrating excellent diagnostic accuracy. We also observed that the effect of endogenous CO2 production related to basal metabolic rates in individuals was statistically insignificant (p = 0.78) on the diagnostic accuracy. However, the presence of H. pylori infection was indicated by the profound effect of urea hydrolysis rate (UHR). Our findings suggest that the current c-PDR (%) is a valid and sufficiently robust novel approach for an accurate, specific, fast and noninvasive diagnosis of H. pylori infection, which could routinely be used for large-scale screening purposes and diagnostic assessment, i.e. for early detection and follow-up of patients.

A residual gas analyzer (RGA) coupled with a high vacuum chamber is described for the non-invasive diagnosis of the Helicobacter pylori (H. pylori) infection through ¹³C-urea breath analysis. The present RGA-based mass spectrometry (MS) method is capable of measuring high-precision ¹³CO₂ isotope enrichments in exhaled breath samples from individuals harboring the H. pylori infection. The system exhibited 100% diagnostic sensitivity, and 93% specificity alongside positive and negative predictive values of 95% and 100%, respectively, compared with invasive endoscopy-based biopsy tests. A statistically sound diagnostic cut-off value for the presence of H. pylori was determined to be 3.0‰ using a receiver operating characteristic curve analysis. The diagnostic accuracy and validity of the results are also supported by optical off-axis integrated cavity output spectroscopy measurements. The δ¹³(DOB)C‰ values of both methods correlated well (R² = 0.9973 at 30 min). The RGA-based instrumental setup described here is simple, robust, easy-to-use and more portable and cost-effective compared to all other currently available detection methods, thus making it a new point-of-care medical diagnostic tool for the purpose of large-scale screening of the H. pylori infection in real time. The RGA-MS technique should have broad applicability for ¹³C-breath tests in a wide range of biomedical research and clinical diagnostics for many other diseases and metabolic disorders.

The article discusses a study which investigated the time-dependent excretion kinetics of 18OO/16O isotope ratios of CO2 in exhalted breath samples for the detection of Helicobacter pylori infection in human stomach. Topics discussed include the use of an optical cavity-enhanced integrated cavity output spectroscopy (ICOS) method and the statistical distribution of 18OO/16O.

We report for the first time the excretion kinetics of the percentage dose of C recovered/h (C-PDR %/h) and cumulative PDR, i.e. c-PDR (%) to accomplish the highest diagnostic accuracy of the C-urea breath test (C-UBT) for the detection of Helicobacter pylori infection without any risk of diagnostic errors using an optical cavity-enhanced integrated cavity output spectroscopy (ICOS) method. An optimal diagnostic cut-off point for the presence of H. pylori infection was determined to be c-PDR (%) = 1.47 % at 60 min, using the receiver operating characteristic curve (ROC) analysis to overcome the 'grey zone' containing false-positive and false-negative results of the C-UBT. The present C-UBT exhibited 100 % diagnostic sensitivity (true-positive rate) and 100 % specificity (true-negative rate) with an accuracy of 100 % compared with invasive endoscopy and biopsy tests. Our c-PDR (%) methodology also manifested both diagnostic positive and negative predictive values of 100 %, demonstrating excellent diagnostic accuracy. We also observed that the effect of endogenous CO production related to basal metabolic rates in individuals was statistically insignificant ( p = 0.78) on the diagnostic accuracy. However, the presence of H. pylori infection was indicated by the profound effect of urea hydrolysis rate (UHR). Our findings suggest that the current c-PDR (%) is a valid and sufficiently robust novel approach for an accurate, specific, fast and noninvasive diagnosis of H. pylori infection, which could routinely be used for large-scale screening purposes and diagnostic assessment, i.e. for early detection and follow-up of patients. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]