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

United European Gastroenterol J. 2019 Jun;7(5):709-715. doi: 10.1177/2050640619826419. Epub 2019 Jan 19.

Abstract

Background: Studies have shown increased intestinal permeability in irritable bowel syndrome. Validating serum biomarkers for altered intestinal permeability in irritable bowel syndrome will facilitate research and pathophysiology-based therapy.

Objective: To measure serum zonulin and intestinal fatty acid binding protein levels in diarrhea-predominant irritable bowel syndrome and constipation-predominant irritable bowel syndrome and compare with healthy controls and celiac disease.

Methods: Serum zonulin and intestinal fatty acid binding protein levels were measured using enzyme-linked immunosorbent assays in constipation-predominant irritable bowel syndrome (n = 50), diarrhea-predominant irritable bowel syndrome (n = 50), celiac disease (n = 53) and healthy controls (n = 42). Irritable bowel syndrome symptom severity was measured using the irritable bowel syndrome-symptom severity scale.

Results: Patients with constipation-predominant irritable bowel syndrome and diarrhea-predominant irritable bowel syndrome had higher zonulin levels compared with healthy controls (p = 0.006 and 0.009 respectively), which was comparable to those with active celiac disease. Although zonulin levels did not correlate with the overall irritable bowel syndrome symptom severity scale, it positively correlated with stool frequency per week (p = 0.03) and dissatisfaction with bowel habits (p = 0.007) in diarrhea-predominant irritable bowel syndrome. Patients with diarrhea-predominant irritable bowel syndrome and constipation-predominant irritable bowel syndrome had lower intestinal fatty acid binding protein levels compared with celiac patients (p = 0.005 and p = 0.047 respectively).

Conclusion: Serum zonulin is upregulated in irritable bowel syndrome and the levels are comparable to those in celiac disease. Zonulin levels correlated with severity of bowel habits in diarrhea-predominant irritable bowel syndrome. Intestinal fatty acid binding protein levels in irritable bowel syndrome patients were not increased suggesting no significant increase in enterocyte death.

Keywords: Intestinal permeability; gut barrier; serine protease; tight junction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / blood
  • Constipation / blood*
  • Diarrhea / blood*
  • Fatty Acid-Binding Proteins / blood
  • Female
  • Haptoglobins
  • Humans
  • Intestinal Mucosa / metabolism
  • Irritable Bowel Syndrome / blood*
  • Irritable Bowel Syndrome / metabolism
  • Male
  • Middle Aged
  • Permeability
  • Protein Precursors / blood*
  • Young Adult

Substances

  • Biomarkers
  • Fatty Acid-Binding Proteins
  • Haptoglobins
  • Protein Precursors
  • zonulin