Serum Zonulin Measured by Commercial Kit Fails to Correlate With Physiologic Measures of Altered Gut Permeability in First Degree Relatives of Crohn's Disease Patients.

Namita Power,Williams Turpin,Michelle I Smith,Osvaldo Espin-Garcia,Kenneth Croitoru

doi:10.3389/fphys.2021.645303

Abstract

Intestinal epithelial cell tight junctions (TJs) contribute to the integrity of the intestinal barrier allowing for control of the physical barrier between external antigens or bacterial products and the internal environment. Zonula occludens-1 (ZO-1) is a protein that modulates intestinal TJs, and serum levels of ZO-1 has been suggested as a biomarker of disrupted barrier function in humans. Previous studies suggested that increased intestinal permeability was associated with evidence of TJ abnormalities. However, there is limited information on the serological measurement of ZO-1 and its relation to other tests of barrier function in healthy subjects. We investigated the correlation of serum ZO-1, with physiologic measures of intestinal permeability (as the ratio of the fractional excretion of lactulose-mannitol or LMR) in a cohort of 39 healthy FDRs of Crohn's disease (CD) patients. No significant correlation was found between LMR and ZO-1 levels (r2 = 0.004, P < 0.71), or intestinal fatty acid binding proteins (I-FABP) (r2 = 0.004, P < 0.71). In conclusion, our data show that ZO-1 and I-FABP are not a marker of gut permeability as defined by LMR.

Highlights

Intestinal permeability is one measure of alterations in gut barrier function in humans
lactulose to mannitol ratio (LMR) ratio is considered as the gold standard to measure gut barrier function (Teshima et al, 2012)
Keita et al (2018) demonstrated that barrier dysfunction as measured by biopsies mounted in Ussing chambers, and tight junction protein expression measured using immunofluorescence, is a primary defect in twin pairs that are discordant for Crohn’s disease (CD)

Summary

Introduction

Intestinal permeability is one measure of alterations in gut barrier function in humans. It has been associated with multiple pathologies such as Crohn’s disease (CD), ulcerative colitis (UC), or celiac disease (Michielan and D’Inca, 2015). Studies have shown that abnormal intestinal permeability is a feature of disrupted intestinal homeostasis and its measurement may be used as a tool to assess gastrointestinal function (Harris et al, 2012; Teixeira et al, 2012; Michielan and D’Inca, 2015; Teshima et al, 2017). Disruption in paracellular permeability and the epithelium may lead to excessive entry of dietary or microbial antigens, which may be a contributing factor for inflammatory diseases or other diseases (Bischoff et al, 2014)

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