Effect of Gluten Ingestion and FODMAP Restriction on Intestinal Epithelial Integrity in Patients with Irritable Bowel Syndrome and Self-Reported Non-Coeliac Gluten Sensitivity

Mol Nutr Food Res. 2021 Mar;65(5):e1901275. doi: 10.1002/mnfr.201901275. Epub 2020 Oct 21.


Scope: Since epithelial barrier dysfunction has been associated with gluten and fermentable oligosaccharide, disaccharide, monosaccharide, and polyols (FODMAPs), the effect of alterations in FODMAP a gluten intake on epithelial barrier function in patients with irritable bowel syndrome (IBS) who self-reported gluten sensitivity.

Methods and results: Circulating concentrations of markers of epithelial injury (syndecan-1 and intestinal fatty acid-binding protein) and bacterial translocation (lipopolysaccharide-binding protein and soluble CD14) are measured while consuming habitual gluten-free diet and during blinded challenges with gluten or placebo on a background of low FODMAP intake. In 33 patients, only syndecan-1 concentrations during their habitual diet are elevated (median 43 ng mL-1 ) compared with 23 ng mL-1 in 49 healthy subjects (p < 0.001). On a low FODMAP diet, symptoms are reduced and levels of syndecan-1 (but not other markers) fell by a median 3335% (p < 0.001) irrespective of whether gluten is present or not.

Conclusion: Gluten ingestion has no specific effect on epithelial integrity or symptoms in this cohort, but reducing FODMAP intake concomitantly reduces symptoms and reverses apparent colonic epithelial injury. These findings highlight the heterogeneity of populations self-reporting gluten sensitivity and implicate FODMAPs in colonic injury in IBS.

Keywords: bacterial translocation; functional bowel disorders; gluten-free diet; intestinal epithelium.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Adult
  • Carrier Proteins / blood
  • Celiac Disease / etiology
  • Diet, Carbohydrate-Restricted
  • Double-Blind Method
  • Female
  • Glutens / administration & dosage*
  • Humans
  • Irritable Bowel Syndrome / diet therapy*
  • Irritable Bowel Syndrome / etiology*
  • Lipopolysaccharide Receptors / blood
  • Malabsorption Syndromes / diet therapy
  • Malabsorption Syndromes / etiology*
  • Male
  • Membrane Glycoproteins / blood
  • Middle Aged
  • Self Report
  • Syndecan-1 / blood
  • Treatment Outcome
  • Young Adult


  • Acute-Phase Proteins
  • CD14 protein, human
  • Carrier Proteins
  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • SDC1 protein, human
  • Syndecan-1
  • lipopolysaccharide-binding protein
  • Glutens