Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2025 Sep 1;31(9):2511-2520.
doi: 10.1093/ibd/izaf043.

Intestinal Permeability In Vivo in Patients With Inflammatory Bowel Disease: Comparison of Active Disease and Remission

Katie A Dunleavy  1 , Chad R Rypstra  1 , Irene Busciglio  1 , Deborah Eckert  1 , Michael Ryks  1 , Ellie Omerdic  1 , Victor G Chedid  1 , Laura E Raffals  1 , Michael Camilleri  1
Affiliations
Comparative Study

Intestinal Permeability In Vivo in Patients With Inflammatory Bowel Disease: Comparison of Active Disease and Remission

Katie A Dunleavy et al. Inflamm Bowel Dis. .

Abstract

Background and aims: Inflammatory bowel disease (IBD) is associated with altered mucus and increased intestinal permeability (IP). Prior reports on permeability in IBD typically used lactulose-to-mannitol ratio (LMR). Food contamination with 12C-mannitol is a significant potential confounder in IP assessment. We aimed to compare small intestinal (SI) and colonic (COL) permeability in IBD, both active (ACT) and in remission (REM), to normal healthy volunteers (NHV).

Methods: Inflammatory bowel disease activity was based on Simple Endoscopic Score for Crohn's Disease (SES-CD) and Mayo endoscopy score for ulcerative colitis (UC). We performed 24-hour IP test using 100 mg 13C-mannitol and 1000 mg lactulose with urine collected during 0-2, 2-8, and 8-24 hours. The primary endpoint was mg excretion of 13C-mannitol and lactulose during 2-24 hours reflecting SI and COL permeability.

Results: Among 17 CD patients, 7 were ACT (SES-CD >6), and 10 REM (SES-CD 0-2). Among 20 UC patients, 10 had ACT (Mayo score 2-3), and 10 REM (Mayo score 0-1). Urinary excretions over 2-24 hours were higher for IBD than NHV: 13C-mannitol (13.8 [IQR 8.8, 18.7] NHV; 18.4 [15.6, 29.9] REM; 19.7 [13.8, 23.6] ACT, P = .003) and lactulose (1.8 [1.3, 3.1] NHV; 3.6 [2.0, 5.0] REM; 3.5 [2.0, 6.6] ACT, P = .006). There was no difference between ACT and REM for any timed urine collection. LMR at 2-24 hours (or 2-8 and 8-24 hours) were not statistically significant between the 3 groups (0.014 [0.010, 0.021] NHV; 0.016 [0.010, 0.023] REM; 0.016 [0.012, 0.038] ACT, P = .237).

Conclusions: Intestinal permeability is increased in IBD using validated in vivo assay relative to NHV; increased IP in IBD persists during remission.

Keywords: IBD; barrier; lactulose; mannitol.

Plain language summary

This paper uses validated methods and documents intestinal barrier dysfunction in patients who have Crohn’s disease or ulcerative colitis and documents the dysfunction when the disease is active or inactive.

PubMed Disclaimer

Conflict of interest statement

K.D., C.D., I.B., M.R., E.O., V.C., and M.C. have no conflict of interests. L.R. has served as a consultant for Bristol Meyers Squibb Company, Fresenius Kabi USA, Geneoscopy, Janssen, and Roivant Sciences.

References

    1. Keita AV, Söderholm JD. The intestinal barrier and its regulation by neuroimmune factors. Neurogastroenterol Motil. 2010;22(7):718-733. doi: https://doi.org/ 10.1111/j.1365-2982.2010.01498.x - DOI - PubMed
    1. Leibovitzh H, Lee S-H, Raygoza Garay JA, et al. ; Crohn’s and Colitis Canada (CCC) Genetic, Environmental, Microbial (GEM) Project Research Consortium. Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn’s disease highlight earliest events of pathogenesis. Gut. 2023;72(8):1462-1471. doi: https://doi.org/ 10.1136/gutjnl-2022-328421 - DOI - PubMed
    1. Dunleavy KA, Raffals LE, Camilleri M. Intestinal barrier dysfunction in inflammatory bowel disease: underpinning pathogenesis and therapeutics. Dig Dis Sci. 2023;68(12):4306-4320. doi: https://doi.org/ 10.1007/s10620-023-08122-w - DOI - PMC - PubMed
    1. Wyatt J, Vogelsang H, Hübl W, Waldhöer T, Lochs H. Intestinal permeability and the prediction of relapse in Crohn’s disease. Lancet. 1993;341(8858):1437-1439. doi: https://doi.org/ 10.1016/0140-6736(93)90882-h - DOI - PubMed
    1. D’Incà R, Di LV, Corrao G, et al. Intestinal permeability test as a predictor of clinical course in Crohn’s disease. Am J Gastroenterol. 1999;94(10):2956-2960. doi: https://doi.org/ 10.1111/j.1572-0241.1999.01444.x - DOI - PubMed

Publication types