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Zonulin in serum as a biomarker fails to identify the IBS, functional dyspepsia and non-coeliac wheat sensitivity
  1. Nicholas J Talley1,
  2. Gerald J Holtmann2,3,
  3. Michael Jones4,
  4. Natasha A Koloski1,3,
  5. Marjorie M Walker5,
  6. Grace Burns1,6,
  7. Michael D E Potter1,
  8. Ayesha Shah3,7,
  9. Simon Keely6,8
  1. 1 Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
  2. 2 School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
  3. 3 Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
  4. 4 Department of Psychology, Macquarie University, Ryde, New South Wales, Australia
  5. 5 Anatomical Pathology, University of Newcastle, Newcastle, New South Wales, Australia
  6. 6 School of Biomedical Science and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia
  7. 7 Faculty of Medicine and Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia
  8. 8 Gastrointestinal Research Group, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
  1. Correspondence to Professor Nicholas J Talley; Nicholas.Talley{at}

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We read with interest the recent work by Stevens et al 1 showing the association between zonulin, fatty acid binding protein 2 (FABP2) and lipopolysaccharide (LPS) plasma levels and increased gut permeability in asymptomatic gastroenterology patients with depression and anxiety disorders, when compared with controls. Zonulin is a regulator of intestinal permeability and a marker of intestinal barrier impairment,2 which is reported in the irritable bowel syndrome (IBS) and functional dyspepsia (FD),3 both of which are associated with anxiety and depression.4 5 The tight junctional protein zonulin (ZO-1) is significantly reduced in these patients possibly driving a low-grade immune response.3 6

The utility of serum zonulin as a biomarker is controversial. One study observed higher serum zonulin levels in coeliac disease (CD) (mean 0.033 ng/mg total proteins), non-coeliac gluten sensitivity (NCGS) (mean 0.030 ng/mg total proteins) and IBS-diarrhoea (mean 0.012 ng/mg total proteins) patients, versus healthy controls,7 but the Malmö Diet and Cancer cardiovascular cohort showed no association between serum zonulin and reported GI symptoms or IBS and FD.8 We aimed to examine serum zonulin as a biomarker for IBS and FD.

Adult participants were recruited from two sources9; (1) a population-based study (n=242; mean age 62.1 (SD=11.9) years; 45.9% female) and (2) a two-site hospital-based study (n=102; mean age 45.0 (SD=16.2) years; 67.4% female). In the population-based study, IBS (n=40) and FD (n=42) were diagnosed according to modified Rome III criteria, while CD (n=6), gluten intolerance (n=6) and NCGS (n=44) had self-reported doctor diagnoses. Healthy controls (n=182) did not meet Rome …

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