Development and Validation of Test for “Leaky Gut” Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults

Background Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion. Aims The aims were as follows: (1) to obtain normative data on small intestinal and colonic permeability; (2) to assess variance on standard 16 g fiber diet performed twice; (3) to determine whether dietary fiber influences gut permeability measurements; and (4) to present pilot data using 2 selected probes in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Methods Sixty healthy female and male adults, age 18–70 years, participated in 3 randomized studies (2 studies on 16.25 g and 1 study on 32.5 g fiber) in otherwise standardized diets. At each test, the following sugars were ingested: 12 C-mannitol, 13 C-mannitol, rhamnose (monosaccharides), sucralose, and lactulose (disaccharides). Standardized meals were administered from 24 hours before and during 24 hours post-sugars with 3 urine collections: 0–2, 2–8, and 8–24 hours. Sugars were measured using high-performance liquid chromatography–tandem mass spectrometry. Eighteen patients with IBS-D underwent 24-hour excretion studies after oral 13 C-mannitol and lactulose. Results Baseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: 12 C-mannitol in all participants; sucralose in 4–8, and rhamnose in 1–3. Median excretions/24 h (percentage of administered dose) for 13 C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. 13 C-mannitol and rhamnose reflected mainly small intestinal permeability. Intraindividual saccharide excretions were consistent, with minor differences with 16.25 g vs 32.5 g fiber diets. Median interindividual coefficient of variation was 76.5% (10–90 percentile: 34.6–111.0). There were no significant effects of sex, age, or body mass index on permeability measurements in health. 13 C-mannitol measurements are feasible in IBS-D. Conclusions Baseline 12 C-mannitol excretion precludes its use; 13 C-mannitol is the preferred probe for small intestinal permeability.