Zonulin-Assessed Intestinal Permeability and Body Composition Changes in Systemic Sclerosis

Background/Objectives: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by endothelial dysfunction, immune system dysregulation, and fibrosis of the skin and internal organs. Gastrointestinal involvement occurs in over 90% of patients and contributes to metabolic alterations and changes in body composition. Given the lack of specific markers of organ damage, zonulin has been investigated as a potential indicator of intestinal permeability. This study aims to evaluate the relationship between intestinal permeability, assessed by zonulin levels, and changes in body composition in SSc patients. Methods: Forty patients meeting EULAR criteria were included. Clinical evaluation, biochemical assessment including zonulin, and body composition analysis using bioelectrical impedance analysis (BIA) were performed. The BIA assessed the following parameters: fat-free mass index (FFMI; kg/m²); body cellular mass index (BCMI); fat mass index (FMI; kg/m²) and visceral fat area (VFA; cm²). Results: 32 of 40 patients enrolled were female (80%) with a median age of 55 years (IQR 49-62.5). Median zonulin level was 0.92 pg/mL (IQR 0.86-1.05). Reduced FFMI was present in 35% of patients and was associated with higher zonulin levels [1.16 pg/mL (IQR 0.91-1.34) vs. 0.92 pg/mL (IQR 0.83-0.96), p < 0.01]. Zonulin correlated negatively with BCMI (r = -0.332, p < 0.05), FFM (r = -0.302, p < 0.05) and muscle mass (r = -0.276, p < 0.05). Conclusions: Elevated serum zonulin levels, reflecting increased intestinal permeability, are associated with adverse body composition changes in SSc, suggesting gut barrier dysfunction as a potential mechanism of muscle loss and a therapeutic target in SSc.