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

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Abstract

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.

Urea breath test without any external urea

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Acknowledgments

M. Pradhan acknowledges the ‘Rapid Grant for Young Investigators (No. BT/PR6683/GBD/27/477/2012)’ from the Department of Biotechnology (DBT, India) for this work. A. Maity, M. Pal and S. Maithani acknowledge the Department of Science & Technology (DST, India) for Inspire Fellowships, whereas S. Som acknowledges Bose Centre for PhD fellowship. We also thank all the volunteers who participated in this study.

Author contributions

Manik Pradhan arranged the funding; Manik Pradhan and Abhijit Maity conceived the study; Manik Pradhan, Sujit Chaudhuri supervised the whole study; Manik Pradhan and Abhijit Maity designed the study; Abhijit Maity, Mithun Pal, Suman Som and Sanchi Maithani collected and analysed the samples; all authors drafted the manuscript and critically reviewed it.

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    Authors and Affiliations

    1. Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata, West Bengal, 700098, India

      Abhijit Maity, Mithun Pal, Suman Som, Sanchi Maithani & Manik Pradhan

    2. Department of Gastroenterology, AMRI Hospital, Salt Lake City, JC-16 & 17, Kolkata, West Bengal, 700098, India

      Sujit Chaudhuri

    3. Technical Research Centre (TRC), S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata, West Bengal, 700098, India

      Manik Pradhan

    Authors
    1. Abhijit Maity
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    2. Mithun Pal
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    3. Suman Som
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    4. Sanchi Maithani
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    5. Sujit Chaudhuri
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    Correspondence to Manik Pradhan.

    Ethics declarations

    The present study has been approved by the Ethics Committee Review Board of AMRI Hospital, Salt Lake, Kolkata, India (Study no.: AMRI/ETHICS/2013/1). All the patients provided their written consent prior to the study.

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    The authors declare no conflict of interests.

    Additional information

    Abhijit Maity and Mithun Pal contributed equally to this work.

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    Maity, A., Pal, M., Som, S. et al. Natural 18O and 13C-urea in gastric juice: a new route for non-invasive detection of ulcers. Anal Bioanal Chem 409, 193–200 (2017). https://doi.org/10.1007/s00216-016-9985-y

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    • DOI: https://doi.org/10.1007/s00216-016-9985-y

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