Zonulin in serum as a biomarker fails to identify the IBS, functional dyspepsia and non-coeliac wheat sensitivity

Talley, Nick; Holtmann, Gerald; Jones, Michael; Koloski, Natasha A.; Walker, Marjorie M.; Burns, Grace; Potter, Michael; Shah, Ayesha; Keely, Simon

doi:10.1136/gutjnl-2019-318664

Cited by 28 publications

(23 citation statements)

References 10 publications

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“…The findings indicate that s-zonulin is associated with diarrhoea and IBS in subjects with morbid obesity. This contrasts to two studies in individuals with lower BMI, which did not find significant associations between s-zonulin levels and gastrointestinal symptoms and disorders [3,30].…”

Section: Fig 1 Inclusion Of Participantscontrasting

confidence: 99%

Changes in serum zonulin in individuals with morbid obesity after weight-loss interventions: a prospective cohort study

Aasbrenn

Lydersen²,

Farup

2020

BMC Endocr Disord

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Background: Zonulin is a biomarker of impaired intestinal permeability, which has been associated with various disorders. The primary aim was to study serum zonulin (s-zonulin) in individuals with morbid obesity before and after a conservative weight loss intervention followed by bariatric surgery. The secondary aims were to explore predictors of s-zonulin, and the associations between the changes of the predictors and changes in s-zonulin, and to compare the associations in the two treatment periods. Methods: Individuals with morbid obesity were included. Data before any weight loss interventions, after a 6 months' conservative weight loss intervention, and 6 months after bariatric surgery were used. S-zonulin was measured with an ELISA method from Immundiagnostik AB, Bensheim, Germany. Data were analysed with mixed models. Results: The mean body mass index was 42.1 kg/m 2 (SD 3.8) at inclusion and was reduced to 38.7 kg/m 2 (SD 3.8) and 29.8 kg/m 2 (SD 3.8) after the conservative treatment and bariatric surgery respectively. S-zonulin was 63 ng/mL (SD 32) at inclusion and was reduced with 19 ng/ml (95% CI 12 to 26, p < 0.001) after conservative treatment and 11 ng/ml (95% CI 0 to 21, p = 0.04) after bariatric surgery. At inclusion, s-zonulin was significantly associated with factors including p-glucose (B = 2.21, 95% CI 1.09 to 3.33, p < 0.001), c-reactive protein (B = 1.02, 95% CI 0.45 to 1.58, p < 0.001) and the intake of proteins (B = 0.23, 95% CI 0.08 to 0.38, p = 0.003) and non-nutritive sweeteners (B = 0.68, 95% CI 0.19 to 1.17, p = 0.007). The reduction in s-zonulin after the conservative weight loss intervention was significantly associated with improvement in diarrhoea (B = 6.6, 95% CI 1.3 to 11.8, p = 0.02), HbA1c (B = 9.7, 95% CI 1.1 to 18.3, p = 0.03), p-glucose (B = 3.5, 95% CI 1.2 to 5.9, p = 0.004) and gamma-GT (B = 0.28, 95% CI 0.09 to 0.47, p = 0.004), but not associated with the change in body mass index (B = 0.9, 95% CI − 1.5 to 3.3, p = 0.46). Conclusions: S-zonulin was markedly reduced after the conservative weight loss intervention, and further reduced after bariatric surgery. The reduction in s-zonulin was associated with improvement of diarrhoea, markers of glucose intolerance and liver disease, but not associated with the change in body mass index.

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Section: Fig 1 Inclusion Of Participantscontrasting

confidence: 99%

Changes in serum zonulin in individuals with morbid obesity after weight-loss interventions: a prospective cohort study

Aasbrenn

Lydersen²,

Farup

2020

BMC Endocr Disord

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“…With great interest we read the work by Talley et al 1 reporting the inadequacy of zonulin as a biomarker due to its failure to identify the irritable bowel syndrome, functional dyspepsia and non-coeliac wheat sensitivity. Zonulin as a biomarker is highly disputed.…”

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confidence: 99%

Blurring the picture in leaky gut research: how shortcomings of zonulin as a biomarker mislead the field of intestinal permeability

Massier¹,

Chakaroun²,

Kovacs³

et al. 2020

Gut

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“…According to their report, the Cusabio kit detects complement factor C3 and haptoglobin; moreover, the kit failed to detect recombinant zonulin. Another study [26] reported that zonulin (unknown manufacture) failed to distinguish between IBS, organic diseases, functional dyspepsia, and healthy populations. Our data confirmed the non- specificity of the Cusabio ELISA kit indicated by Ajamian and colleagues [25], as verified by HP genotyping.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent studies [24,25] showed that these kits (for instance Immundiagnostik and Cusabio), do not detect zonulin, but haptoglobin and complement factor C3 [25]. Other studies have shown that zonulin failed to identify conditions where small intestinal permeability is a known feature [24][25][26]. Intriguingly, no study has addressed both human colonic permeability and the levels of zonulin in parallel.…”

Section: Introductionmentioning

confidence: 99%

Colonic paracellular permeability and circulating zonulin-related proteins

de-Faria

Bednarska

Ström

et al. 2021

Scandinavian Journal of Gastroenterology

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Objective: Irritable bowel syndrome (IBS) is a gut-brain disorder associated with increased gut permeability. Zonulin has been suggested to regulate the gut barrier and claimed to be pre-haptoglobin 2 (pre-HP2) and circulating zonulin is often used as a proxy for gastrointestinal permeability. This study investigated the correlation between colonic paracellular permeability and levels of circulating zonulin and pre-HP2. Materials and Methods: Colonic biopsies from 32 patients with IBS and 15 healthy controls (HC) were used to measure permeability in Ussing chambers and levels of zonulin (Cusabio ELISA). Zonulin was also measured in blood samples from 40 HC, 78 patients with IBS and 20 patients with celiac disease (CeD), before and after a gluten-free diet. In addition, we verified HP genotype and circulating pre-HP2 using a monoclonal pre-HP2 antibody (Bio-Rad) by ELISA. Results: Increased colonic paracellular permeability correlated positively with zonulin levels in IBS biopsies, but negatively with plasma zonulin. We found no agreement between circulating zonulin and pre-HP2. Genotyping revealed non-specificity of the zonulin kit, as all pre-HP2 non-producers presented detectable levels. Patients with CeD displayed higher pre-HP2 and zonulin levels compared to HC. A gluten-free diet in patients with CeD led to lower serum zonulin and pre-HP2 concentrations. Conclusions: Our study suggests that neither circulating zonulin nor pre-HP2 mirror colonic permeability. Our data corroborate previous reports showing the inability of the Cusabio zonulin kit to target zonulin and highlights that the results of studies using this kit must be reexamined with caution.

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Zonulin in serum as a biomarker fails to identify the IBS, functional dyspepsia and non-coeliac wheat sensitivity

Cited by 28 publications

References 10 publications

Changes in serum zonulin in individuals with morbid obesity after weight-loss interventions: a prospective cohort study

Changes in serum zonulin in individuals with morbid obesity after weight-loss interventions: a prospective cohort study

Blurring the picture in leaky gut research: how shortcomings of zonulin as a biomarker mislead the field of intestinal permeability

Colonic paracellular permeability and circulating zonulin-related proteins

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