Exploring Triple-Isotopic Signatures of Water in Human Exhaled Breath, Gastric Fluid, and Drinking Water Using Integrated Cavity Output Spectroscopy

Water, the major body fluid in humans, has four main naturally occurring isotopologues, H₂¹⁶O, H₂¹⁷O, H₂¹⁸O, and H²H¹⁶O (i.e., HD¹⁶O) with different masses. The underlying mechanisms of the isotope-specific water-metabolism in the human gastrointestinal (GI) tract and respiratory system are largely unknown and remained illusive for several decades. Here, a new strategy has been demonstrated that provides direct quantitative experimental evidence of triple-isotopic signatures of water-metabolism in the human body in response to the individual’s water intake habit. The distribution of water isotopes has been monitored in drinking water (DW; δD = −36.59 ± 10.64‰ (SD), δ¹⁸O = −5.41 ± 1.47‰ (SD), and δ¹⁷O = −2.92 ± 0.79‰ (SD)), GI fluid (GF; δD = −35.91 ± 7.30‰ (SD), δ¹⁸O = −3.98 ± 1.29‰ (SD), and δ¹⁷O = −2.37 ± 0.57‰ (SD)), and human exhaled breath (EB; δD = −119.63 ± 7.27‰ (SD), δ¹⁸O = −13.69 ± 1.23‰ (SD), and δ¹⁷O = −8.77 ± 0.98‰ (SD)) using a laser-based off-axis integrated cavity output spectroscopy (OA-ICOS) technique. This study explored a new analytical method to disentangle the competing effects of isotopic fractionations of water during respiration in humans. In addition, our findings revealed that deuterium-enriched exhaled semiheavy water, i.e., HD¹⁶O is a new marker of the noninvasive assessment of the ulcer-causing H. pylori gastric pathogen. We also clearly showed that the water-metabolism-derived triple-isotopic compositions due to impaired water absorption in the GI tract can be used as unique tracers to track the onset of various GI dysfunctions. These findings are thus bringing a new analytical methodology to better understand the isotope-selective water-metabolism that will have enormous applications for clinical testing purposes.