Zonulin and I-FABP are markers of enterocyte damage in celiac disease

Aim. To evaluate the level of serum I-FABP (Fatty-Acid-Binding Protein – a protein that binds fatty acids) and fecal zonulin as markers of the permeability of the mucous membrane of the small intestine in celiac patients.

Materials and methods. A total of 151 celiac patients (25 men and 126 women) were examined. The median age was 42 years. Group I included 58 patients with newly diagnosed celiac disease; in group 2 – 38 patients, knowingly or unknowingly violating the gluten-free diet; group 3 consisted of 55 patients strictly observing gluten-free diet. The control group consisted of 20 healthy volunteers: 4 men and 16 women. All patients underwent esophagogastroduodenoscopy by biopsy of the mucous membrane of the small intestine and assessment of duodenobioptates according to Marsh. In the blood serum, the level of antibodies to tissue transglutaminase IgA and IgG was determined by the enzyme-linked immunosorbent assay using kits manufactured by Orgentec Diagnostics GmbH (Germany), the concentration of I-FABP in blood serum was determined using Hycult Biotech kits (Netherlands). The content of zonulin in feces was investigated by enzyme-linked immunosorbent assay using kits from Immundiagnostik AG (Germany). Statistical analysis was performed using the Statistica 13.3 software (StatSoft Inc., USA).

Results. There was a significant increase in the level of antibodies to tissue transglutaminase IgA [120.0 (41.1–200)] IU/ml and IgG [31.4 (5.5–78.9)] IU/ml in patients of group 1 compared with group 2 [IgA 9.1 (2.9–87.6)] and IgG [3.8 (2.2–19.7)] IU/ml and group 3 [IgA 1.6 (1.0–3.2)] and IgG [2.2 (1.15–2.53)] (p<0.01). The level of I-FABP in blood serum in patients of group 1 averaged 2045 pg/ml, in patients in group 2 – 1406 pg/ml, in patients in group 3 – 1000 pg/ml. All patients showed a significant increase in the mean I-FABP values compared to controls (1, 2 and control – p<0.01, 3 and control – p=0.016). In patients with Marsh grade III A–C atrophy, the I-FABP level depended on the degree of damage to the mucosa and significantly differed from the control: March IIIA (median: 1310 pg/ml, interquartile range: 1212–1461 pg/ml), March IIIB (median: 2090 pg/ml, interquartile range: 1812–2322 pg/ml) as well as Marsh IIIC (median: 2058 pg/ml, interquartile range 1858–2678 pg/ml). The concentration of zonulin in feces in patients of group 1 averaged 111.6 pg/mg, in patients of group 2 – 90.5 pg/mg. In patients of group 3 – 50 IU/ml. The concentration of zonulin in feces increased as the degree of mucosa atrophy increased (r=0.585, p<0.01). However, despite the fact that both of these markers may indicate impaired permeability, each of them indicates damage to a certain level of the intestinal barrier, which is not always associated with the degree of mucosa atrophy.

Conclusion. Determination of serum I-FABP and fecal zonulin levels in celiac patients allows for the assessment of intestinal permeability and can serve as non-invasive markers for monitoring ongoing structural changes in the mucosa without the need for endoscopy.