Fecal Zonulin as a Non-Invasive Marker of Intestinal Permeability: Findings from a Prospective Cohort Study

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as part of the broader spectrum of metabolic disorders, with links to obesity, insulin resistance, and systemic inflammation. Emerging evidence points to a role of the gut–liver axis, particularly intestinal permeability, in its pathogenesis. Zonulin—a regulator of tight junctions—has been proposed as a marker of impaired barrier function, but its relevance in MASLD remains unclear. Methods: We conducted a prospective observational study including 52 adult patients diagnosed with MASLD. Hepatic steatosis was evaluated using the SteatoTest (FibroMax panel), while fecal zonulin levels were measured by ELISA at baseline. Clinical, anthropometric, and metabolic parameters were assessed. We used ROC curve analysis to explore zonulin’s predictive value for moderate-to-severe steatosis (≥S2). Results: Fecal zonulin levels above 107 ng/mL were found in 26.9% of participants. This group showed a higher frequency of moderate-to-severe steatosis (78.6%) compared to those with lower zonulin levels (55.3%), although the correlation with SteatoTest was weak (r = 0.19, p > 0.05). No significant associations were found between zonulin and liver fibrosis, insulin resistance (HOMA-IR), or the BARD score. The AUC for detecting steatosis ≥ S2 was 0.68. Conclusions: Although limited as a standalone diagnostic tool, fecal zonulin may reflect underlying gut barrier dysfunction in MASLD and show moderate association with hepatic steatosis. Its role as a complementary biomarker in non-invasive stratification frameworks warrants further study, especially in larger cohorts with control groups.