Coeliac disease and the intestinal barrier: mechanisms of disruption and strategies for restoration.

This review examines the role of intestinal barrier dysfunction in coeliac disease (CD), a condition in which genetically predisposed individuals mount an immune-mediated response to dietary gluten that damages the small intestine. The authors explore the evidence that increased intestinal permeability is a central feature of CD pathophysiology, detailing the contributing mechanisms: dysregulation of the protein zonulin, pro-inflammatory cytokines, alterations in gut microbiota, and immune responses to gliadin peptides. The review then comprehensively surveys therapeutic strategies aimed at restoring barrier integrity, including dietary interventions, nutritional supplements, and investigational pharmacological agents such as larazotide acetate (a tight-junction regulator) and IMU-856 (a SIRT6 activator targeting mucosal regeneration). The authors also highlight a key limitation in the field: the absence of validated, reliable biomarkers for accurately measuring intestinal permeability in CD. They advocate for further research into barrier-restoring therapies, particularly as adjuncts to a gluten-free diet for maintaining disease remission. As a narrative review, the paper synthesises existing literature but does not generate new primary data, and conclusions are subject to the quality and heterogeneity of the underlying studies.

Why this grade: This is a narrative review synthesising existing literature on coeliac disease and intestinal permeability; it generates no new primary data, so evidence grading reflects the review classification rather than direct experimental findings.