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Pubmed-Development and Validation of Test for "Leaky Gut" Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults


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Gastroenterology. 2021 Apr 15:S0016-5085(21)00642-9. doi: 10.1053/j.gastro.2021.04.020. Online ahead of print.

ABSTRACT

BACKGROUND: Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion.

AIMS: 1. To obtain normative data on small intestinal and colonic permeability; 2. To assess variance on standard 16g fiber diet performed twice; 3. To determine whether dietary fiber influences gut permeability measurements; 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 18-70y, participated in 3 randomized studies (2 studies on 16.25g and 1 on 32.5g 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 24h before and during 24h post-sugars with 3 urine collections: 0-2, 2-8, and 8-24h. Sugars were measured by HPLC-MS. Eighteen patients with IBS-D underwent 24h 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, rhamnose in 1-3. Median excretions/24h (% of administered dose) for 13C-mannitol, rhamnose, lactulose and sucralose were respectively ∼30%, ∼15%, 0.32% and 2.3%. 13C-mannitol and rhamnose reflected mainly small intestinal permeability. Intra-individual saccharide excretions were consistent, with minor differences with 16.25g vs. 32.5g fiber diets. Median COVinter was 76.5% (10-90%ile: 34.6-111.0). There were no significant effects of sex, age, or BMI on permeability measurements in health. 13C-mannitol measurements are feasible in IBS-D.

CONCLUSION: Baseline 12C-mannitol excretion precludes its use; 13C-mannitol is the preferred probe for small intestinal permeability.

PMID:33865841 | DOI:10.1053/j.gastro.2021.04.020

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