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

Katayoun Khoshbin, Lehar Khanna, Daniel Maselli, Jessica Atieh, Margaret Breen-Lyles, Kayla Arndt, Deborah Rhoten, Roy B. Dyer, Ravinder J. Singh, Sunita Nayar, Sandra Bjerkness, William S. Harmsen, Irene Busciglio, Michael Camilleri

Research output: Contribution to journalArticlepeer-review


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: 12C-mannitol, 13C-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 13C-mannitol and lactulose. Results: Baseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: 12C-mannitol in all participants; sucralose in 4–8, and rhamnose in 1–3. Median excretions/24 h (percentage of administered dose) for 13C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. 13C-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. 13C-mannitol measurements are feasible in IBS-D. Conclusions: Baseline 12C-mannitol excretion precludes its use; 13C-mannitol is the preferred probe for small intestinal permeability.

Original languageEnglish (US)
Pages (from-to)463-475.e13
Issue number2
StatePublished - Aug 2021


  • Barrier
  • Lactulose
  • Mannitol
  • Sucralose

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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