Celiac DiseaseGut Barrier DysfunctionI-FABP BiomarkerIBS-CIBS-D

Serum zonulin is elevated in IBS and correlates with stool frequency in IBS-D

Why this matters for your gut health

Irritable bowel syndrome (IBS) affects roughly 11% of adults worldwide and significantly impacts quality of life, yet the biological mechanisms behind it — particularly altered intestinal permeability (“leaky gut”) — have been hard to measure reliably. Existing tests (like the lactulose-mannitol assay or intestinal biopsies) are invasive, time-consuming, or unreliable. Identifying a simple blood-based biomarker like zonulin could make diagnosis and future targeted treatment more practical and accessible.

Summary

The study compared serum zonulin and intestinal fatty acid binding protein (I-FABP) levels across four groups: diarrhea-predominant IBS (IBS-D, n=50), constipation-predominant IBS (IBS-C, n=50), celiac disease (n=53), and healthy controls (n=42). Zonulin levels were significantly higher in both IBS-D and IBS-C compared to healthy controls, and were comparable to levels seen in active celiac disease. I-FABP levels, however, were not elevated in IBS patients, suggesting no significant enterocyte (intestinal cell) damage — differentiating the mechanism of permeability change in IBS from that in celiac disease.

Key findings

  • Serum zonulin was significantly higher in IBS-D and IBS-C than in healthy controls (p=0.009 and p=0.006 respectively).
  • Zonulin levels in IBS patients were statistically comparable to those in active celiac disease.
  • Zonulin positively correlated with stool frequency (p=0.03) and dissatisfaction with bowel habits (p=0.007) specifically in IBS-D patients.
  • Zonulin did not correlate with overall IBS symptom severity (IBS-SSS).
  • I-FABP levels were lower in IBS-D and IBS-C compared to celiac disease, indicating minimal enterocyte turnover/damage in IBS.
  • Findings suggest tight junction (gut barrier) dysfunction occurs in IBS despite normal small bowel histology.

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Citation

Singh P, Silvester J, Chen X, Xu H, Sawhney V, Rangan V, Iturrino J, Nee J, Duerksen DR, Lembo A. Serum zonulin is elevated in IBS and correlates with stool frequency in IBS-D. United European Gastroenterology Journal. 2019;7(5):709-715. doi:10.1177/2050640619826419

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