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

The C-urea breath test (C-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 C-UBT has numerous limitations, drawbacks and pitfalls owing to the ingestion of C-labelled external urea. Here, we show that H. pylori is able to utilize the natural C and O-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 C and O-isotopic fractionations of breath CO 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 C-enriched external urea. This deepens our understanding of the UBT exploiting the natural C and O-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 C-enriched urea for treating these common diseases by a single breath test. Graphical Abstract Urea breath test without any external urea.