Assessment of Small Intestinal Permeability using 1H-NMR Spectroscopy

Abstract

Background: Evaluation of small intestinal permeability (SIP) is based on the estimation of the urinary excretion ratio of a large and a small molecule (lactulose and mannitol, L/M) after oral administration. We evaluated SIP using 1H-NMR spectroscopy.

Methods: In-vitro experiments on known concentration of mannitol and lactulose solutions were performed to measure accuracy and precession of quantification using 1H-NMR spectroscopy. Eighteen patients with malabsorption syndrome (MAS) and 28 healthy subjects (HS) underwent SIP evaluation using L/M excretion ratio over 6-h after oral administration of 15 mL (10g) lactulose and 5 g mannitol using 1H-NMR spectroscopy and trimethyl silyl propionic acid as external reference and for quantification.

Results: Median errors of estimation of mannitol and lactulose were 5% (range 1.2 to 5) and 1.3% (range 0.2 to 1.3), respectively in-vitro. Patients with MAS excreted higher quantity of lactulose in urine than HS (median 0.33 mmol vs 0.12, 0 to .676 mmol, p<0.008). There was a trend towards lower urinary excretion of mannitol in patients with MAS than HS (median 3.58, range 0.61 to 15.77 mmol vs. 3.82, 1.34 to 16.42 mmol, p = ns). L/M ratio was higher among patients with MAS as compared to HS (median 0.1172 vs 0.045, p< 0.002). A cut-off value of L/M excretion ratio by receiver-operating characteristic (ROC) curve of 0.049 had a sensitivity and specificity of 72% and 61%, respectively; a cut-off value of 0.078 had a specificity of 90% but low sensitivity (67%). Area under ROC curve was 0.77.

Conclusion: 1H-NMR spectroscopy is an analytical tool for assessment of SIP with reasonable sensitivity and specificity.