PP403 - URINARY ¹⁵N-NITRATE PRODUCTION FROM ORAL ¹⁵N-ARGININE AS A MARKER FOR SMALL INTESTINAL INFLAMMATION IN ZAMBIAN ADULTS WITH ENVIRONMENTAL ENTEROPATHY

PP403

URINARY ¹⁵N-NITRATE PRODUCTION FROM ORAL ¹⁵N-ARGININE AS A MARKER FOR SMALL INTESTINAL INFLAMMATION IN ZAMBIAN ADULTS WITH ENVIRONMENTAL ENTEROPATHY

J. W. Weatherill^1,*, E. McKay¹, P. Kelly^2,3, D. J. Morrsion¹

¹SUERC, University of Glasgow, Glasgow, United Kingdom, ²Tropical Gastroenterology & Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia, ³Blizard Institute, Queen Mary University of London Barts and The London School of Medicine and Dentistry, London, United Kingdom

Rationale: Environmental enteropathy (EE) is characterised by morphological changes, gut barrier dysfunction and inflammation. Here we assess the utility of ultrasensitive ¹⁵N-tracer methodology to assess gut inflammation in EE non-invasively.

Methods: The GI Tools study recruited 96 adults from Lusaka, Zambia (80 low-SES, 16 high SES), who were assessed for gut permeability (lactulose:rhamnose (LRR)), gut damage (iFABP) and inflammation (sCD14). Oral ¹⁵N₂-arginine was also administered (dose: 1.7 mg) and ¹⁵NO₃ isotopologues measured by Orbitrap isotope ratio mass spectrometry (IRMS). Baseline urine was collected prior to ¹⁵N₂-arginine administration and at 180 mins. Urine was diluted (1:100, ACN/MeOH) and analysed on an Orbitrap Exploris™ 480 MS (20 min; 61-65 m/z). Sample injections were bracketed by a reference standard (USGS35) to produce absolute δ¹⁵NO₃ values at baseline. Δ¹⁵NO₃, defined as δ¹⁵NO₃ (180 min – baseline), represents ¹⁵NO₃ enrichment from ¹⁵N₂-arginine through intermediary ¹⁵NO.

Results: Baseline δ¹⁵NO₃ and Δ¹⁵NO₃ were assessed in 64 low-SES and 16 high-SES participants indicating measurable conversion of ¹⁵N₂-arginine to urinary ¹⁵NO₃ (Table 1). The data were correlated with indicators of gut inflammation. Urinary Δ¹⁵NO₃ showed positive correlations with iFABP (r=0.39; p=0.002) and LRR (r=0.39; p=0.015) in the low-SES group and sCD14 (r=0.69; p=0.004) in the high-SES group. Baseline δ¹⁵NO₃ was also correlated with LRR (r=-0.46; p=0.003).

Table 1: Urine Δ¹⁵NO₃ values

* p = 0.0002

Conclusion: This simple, non-invasive test shows the potential of urinary ¹⁵NO₃ as a marker for localised small intestinal inflammation. Ultrasensitive Orbitrap IRMS facilitates minimal tracer dosing and minimal sample requirements potentially enabling routine studies in children and vulnerable patient groups.

Disclosure of Interest: None declared