Fecal Zonulin as a Potential Biomarker of Intestinal Barrier Dysfunction in Obesity: Molecular Mechanisms, Clinical Validation, and Methodological Challenges - Review of Literature

Abstract

Introduction: Intestinal permeability is a tightly regulated physiological process that enables the transport of nutrients and ions while preventing the passage of harmful luminal antigens. The term "leaky gut" is often misused in pseudoscientific contexts, despite the existence of well-established physiological mechanisms regulating epithelial barrier function. In obesity, chronic low-grade inflammation and gut dysbiosis stimulate the secretion of zonulin, a physiological modulator of tight junctions (TJs). Increased zonulin levels promote pathological disruption of the leak pathway, contributing to systemic low-grade inflammation. Assessment of intestinal barrier integrity may have clinical value in evaluating metabolic risk and monitoring subclinical inflammation.

Methods: A literature search was conducted using the PubMed/MEDLINE and Google Scholar databases. Publications addressing zonulin, intestinal permeability, obesity, fecal biomarkers, epithelial transport mechanisms, ELISA assay specificity, and clinical correlations were reviewed.

Results: Higher fecal zonulin concentrations were consistently associated with increased body mass index (BMI). Clinical studies demonstrated a direct relationship between impaired intestinal barrier integrity and systemic low-grade inflammation. Weight loss improved intestinal epithelial integrity and was accompanied by favorable changes in gut microbiota composition.

Conclusions: Increased intestinal permeability in obesity is a pathological consequence of tight junction dysfunction. Fecal zonulin is a validated, non-invasive biomarker of intestinal barrier impairment and may be useful for monitoring the effectiveness of metabolic interventions. However, its routine clinical application remains limited due to the need for further standardization and validation.