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Natural 18O and 13C-urea in gastric juice: a new route for non-invasive detection of ulcers

Maity, Abhijit, Pal, Mithun, Som, Suman, Maithani, Sanchi, Chaudhuri, Sujit, Pradhan, Manik
Analytical and bioanalytical chemistry 2017 v.409 no.1 pp. 193-200
Helicobacter pylori, breath tests, carbon dioxide, cost effectiveness, duodenal ulcers, enzyme activity, gastric juice, humans, indigestion, ingestion, juices, oral administration, pathogenesis, pathogens, stable isotopes, urea, urease
The ¹³C-urea breath test (¹³C-UBT), developed a few decades ago, is widely used as a non-invasive diagnostic method to detect only the presence of the gastric pathogen Helicobacter pylori infection; however, the actual disease state, i.e. whether the person harbouring H. pylori has peptic ulcer disease (PUD) or non-ulcerous dyspepsia (NUD), is still poorly understood. Nevertheless, the present ¹³C-UBT has numerous limitations, drawbacks and pitfalls owing to the ingestion of ¹³C-labelled external urea. Here, we show that H. pylori is able to utilize the natural ¹³C and ¹⁸O-urea inherently present in the gastric juice in humans for its urease activity which has never been explored before. In vitro measurements of isotopic fractionations of gastric juice urea provide new insights into the actual state of the infection of PUD or NUD. We also provide evidence of the unusual ¹³C and ¹⁸O-isotopic fractionations of breath CO₂ that are distinctively altered in individuals with PUD encompassing both gastric and duodenal ulcers as well as with NUD by the enzymatic activity of H. pylori in the gastric niche without oral administration of any ¹³C-enriched external urea. This deepens our understanding of the UBT exploiting the natural ¹³C and ¹⁸O-gastric juice urea in the pathogenesis of H. pylori infection, reveals the actual disease state of PUD or NUD and thus offers novel opportunities for a simple, robust, cost-effective and non-toxic global strategy devoid of any ¹³C-enriched urea for treating these common diseases by a single breath test. Graphical Abstract Urea breath test without any external urea