Table 4.
Summary of in vivo measurements of intestinal permeability in humans, focusing on studies that include noninflammatory disease
| Reference | Year | Method | Patients with IBS and Controls, n | IP of Patients with IBS, % above normal or LMR | Comments |
|---|---|---|---|---|---|
| Strobel et al. (194) | 1984 | C/M | 15 IBS and 10 controls | Mean ratio: 0.024 (normal 0.037) | Nonbiopsied volunteers as controls |
| Lobley et al. (130) | 1990 | Raffinose/l-arabinose | 62 IBS and 40 controls | Mean ratio: 0.016 (normal 0.015) | No significant difference in IP between IBS and controls |
| Barau and Dupont (8) | 1990 | L/M | 17 IBS and 39 controls (children) | 47 vs. 0% above normal for IBS vs. controls, respectively (normal <0.0245) | Threshold of normal defined by a control group of children without IBS |
| Vogelsang et al. (219) | 1995 | L/M | 40 symptomatic and 30 controls | 30% of symptomatic patients above normal (>0.030) | Patients with “nonspecific” GI symptoms |
| Dainese et al. (37) | 1999 | L/M | 33 IBS and 0 controls | 12% IBS above normal (>0.025) | IP normal in 88% of subjects |
| Berstad et al. (15) | 2000 | 51Cr-EDTA | 18 IBS and 0 controls | Excretion: 0.07% in IBS | Patients with IBS (abdominal pain and/or diarrhea) used as controls in IBD study |
| Spiller et al. (190) | 2000 | L/M | 10 PI-IBS, 21 acute Campylobacter enteritis, and 12 controls | 50% IBS vs. 12 controls; mean LMR: 0.060; range: 0.008–0.22 (normal <0.03) | Increased IP in subset of patients with PI-IBS compared with asymptomatic controls |
| Tibble et al. (205) | 2002 | L/R | 339 IBS and 263 organic disease | Mean ratio: 0.028; range: 0.005–0.216 (normal <0.05) | Permeability of small intestine close to normal in IBS |
| Marshall et al. (137) | 2004 | L/M | 132 IBS and 86 controls | 35.6 vs. 18.6% above normal for IBS vs. controls, respectively (>0.020 LMR) | After outbreak of acute gastroenteritis, SB IP was slightly elevated in IBS (no difference between PI-IBS and non-PI-IBS) |
| Dunlop et al. (51) | 2006 | 51Cr-EDTA | 15 IBS-D + 15 IBS-C with 15 controls and 15 PI-IBS + 15 non-PI-IBS with 12 controls | Excretion: in proximal SB: 0.19% IBS-D, 0.085% IBS-C, 0.07% controls; in SB: 0.43% PI-IBS, 0.84% non-PI-IBS, 0.27% controls | There were 2 studies: 1 comparing IBS-D and IBS-C vs. controls and 1 comparing PI-IBS and non-PI-IBS with IBS-D vs. controls; there may be subtle differences in IP between IBS subgroups |
| Shulman et al. (180) | 2008 | L/M and S/L | 109 Children with IBS or functional abdominal pain and 66 controls | Increased SB and colonic permeability | No correlation between GI permeability and pain-related symptom or stool form |
| Park et al. (157) | 2009 | PEG 3,350-to-PEG 400 ratio by HPLC | 38 IBS (all subtypes) and 12 healthy controls | Increased in whole IBS group | No relationship of increased permeability and positive L breath test |
| Zhou et al. (238) | 2009 | L/M | 54 IBS-D and 22 controls | Increased LMR in 39% of patients | Relationship to increased abdominal pain and visceral and thermal sensitivity |
| Kerckhoffs et al. (113) | 2010 | PEG | 14 IBS (all subtypes) and 15 healthy controls | No difference between IBS and healthy controls | NSAIDs increase permeability more in IBS than in healthy controls |
| Zhou et al. (237) | 2010 | L/M | 19 IBS-D and 10 controls | Increased in 42% of patients | |
| Rao et al. (172) | 2011 | L/M | 12 IBS-D, 12 healthy, and 10 inactive or treated UC or microscopic colitis | Increased urine M excretion at 0–2 and 2–8 h and L excretion at 8–24 h in IBS-D | Demonstrated validity of individual sugar excretion as well as LMR |
| Gecse et al. (74) | 2012 | 51Cr-EDTA | 18 IBS-D, 12 IBS-C, 13 inactive UC, and 10 healthy | Decreased in proximal small intestine of IBS-C; increased in colon of IBS-D | Elevated gut permeability is localized to the colon both in IBS-D and in inactive UC |
| Vazquez-Roque et al. (214) | 2013 | L/M | 45 IBS-D: trial of ±gluten diets | GCD increased SB permeability (based on M and LMR); no increase in colon permeability | GCD significantly decreased expression of ZO-1, claudin-1, and occludin in rectosigmoid mucosa; all effects of gluten were greater in patients positive for HLA DQ2/8 |
| Del Valle-Pinero et al. (41) | 2013 | 4 probes: S, sucrose, M, and L | 20 IBS and 39 matched healthy controls | Colonic permeability significantly lower in IBS compared with healthy controls, shown by lower S excretion in IBS compared with controls | IBS subgroups not specified |
| Turcotte et al. (207) | 2013 | Confocal laser endomicroscopy | 16 IBS and 18 healthy controls | Median epithelial gap densities for controls and IBS were 6 and 32 gaps per 1,000 epithelial cells, respectively | Median difference in gap density between IBS and controls was 26 (95% CI: 12–39) gaps per 1,000 cells; small effects of age and sex |
| Fritscher-Ravens et al. (65) | 2014 | Confocal laser endomicroscopy | 36 IBS with suspected food intolerance | No overall differences, but positive results in 22 of 36 patients: increased number of IELs, formation of epithelial leaks/gaps, and intervillous spaces widened | Diluted food antigens administered directly to the duodenal mucosa; however, no correlation with conventional histology |
| Mujagic et al. (145) | 2014 | Sucrose excretion and LRR in 0–5-h urine; 0–24- and 5–24-h S-to-erythritol ratio | 34 IBS-D, 21 IBS-C, 30 IBS-M, 6 IBS-U, and 94 healthy controls | The 0–5-h LRR only different in IBS-D vs. healthy controls; no other differences in gastroduodenal or colonic permeability | Analysis adjusted for age, sex, BMI, anxiety or depression, smoking, alcohol intake, and use of medication |
| Peters et al. (165) | 2017 | L/13C-M, mucosal impedance, and serum LPS | 19 IBS-C and 18 healthy volunteers | Normal SB and colonic permeability in IBS-C | Concordant results (normal) using duodenal mucosal impedance, ex vivo barrier measurements, and colonic mucosal expression of occludin, ZO-1, 2, and 3, and claudin genes |
| Edogawa et al. (53) | 2018 | L/13C-M | 9 healthy volunteers | Increased L SB permeability by indomethacin, recovered to baseline 4–6 wk later | Only women demonstrated decreased fecal microbial diversity, including an increase in Prevotella abundance, after indomethacin |
| Linsalata et al. (128) | 2018 | urinary sucrose, L, and M over 5 h and circulating biomarkers | 39 IBS-D and 20 healthy volunteers | There were 2 distinct IBS-D subtypes identified, 1 with increased L, sucrose excretion, and I-FABP and DAO levels, suggesting increased permeability of small intestine | Inflammatory parameters and markers of bacterial translocation (IL-6 and LPS) were significantly higher in IBS-D with increased permeability of small intestine |
Here, n = no. of subjects. BMI, body mass index; C, cellobiose; CI, confidence interval; 13C-M, [13C]mannitol; 51Cr-EDTA, chromium-labeled EDTA; DAO, diamine oxidase; GCD, gluten-containing diet; GI, gastrointestinal; HLA DQ2/8, human leukocyte antigen DQ2 or DQ8; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; IBS-C, IBS with constipation; IBS-D, IBS with diarrhea; IBS-M, IBS with mixed bowel habits; IBS-U, unsubtyped IBS; IELs, intraepithelial lymphocytes; I-FABP, intestinal fatty acid-binding protein; IP, intestinal permeability; L, lactulose; LMR, lactulose-to-mannitol ratio; LRR, lactulose-to-rhamnose ratio; M, mannitol; PEG, polyethylene glycol; PI-IBS, postinfectious IBS; R, rhamnose; S, sucralose; SB, small bowel; UC, ulcerative colitis; ZO-1, zonula occludens-1.