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

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.