Elucidating the Significance of Zonulin in the Pathogenesis of Chronic Inflammatory Disorders: Emphasis on Intestinal Barrier Function and Tight Junction Regulation

Abstract: The intestinal barrier, a critical component of the body's defense system, plays a vital role in maintaining homeostasis by preventing the translocation of harmful substances from the gut lumen into the bloodstream. Disruptions in this barrier, often characterized by increased intestinal permeability, are increasingly recognized as contributors to the development and progression of various Chronic Inflammatory Disorders (CIDs). Zonulin, a key regulator of intestinal Tight Junctions (TJs), has emerged as a pivotal player in this process. Dysregulation of zonulin, leading to increased intestinal permeability, has been implicated in the pathogenesis of a wide range of CIDs, including Inflammatory Bowel Disease (IBD), celiac disease, and Multiple Sclerosis (MS). This review examines the intricate relationship between zonulin and intestinal permeability, emphasizing its role in regulating TJ integrity and its association with various CIDs. Recent research has demonstrated the therapeutic potential of targeting zonulin, specifically through the use of larazotide acetate, a zonulin antagonist. Preclinical and clinical studies have shown promising results in improving gut barrier integrity and reducing inflammation in patients with CIDs. These findings underscore the significance of zonulin as a potential biomarker for intestinal barrier function and a promising therapeutic target for managing CIDs. Further research is needed to elucidate the precise mechanisms of action of zonulin antagonists and evaluate their efficacy and safety in clinical trials. A deeper understanding of the complex interplay among zonulin, intestinal permeability, and CIDs is crucial, paving the way for novel therapeutic strategies and personalized approaches to patient care.