Effects of probiotic supplementation on serum zonulin levels in patients with chronic kidney disease: a randomized clinical trial

Abstract Introduction: Chronic kidney disease (CKD) is associated with intestinal dysbiosis, systemic inflammation, and impaired intestinal barrier function. Serum zonulin has been proposed as an indirect marker of intestinal permeability, although its clinical relevance in CKD remains uncertain. Objective: To evaluate the effect of probiotic supplementation on serum zonulin levels in patients undergoing maintenance hemodialysis. Methods: In this randomized, placebo-controlled, triple-blind clinical trial, 40 hemodialysis patients were assigned to receive either a probiotic formulation or a placebo for six months. The primary outcome was the between-group difference in change in serum zonulin from baseline to follow-up. Secondary outcomes included metabolic, anthropometric, hemodynamic, and gastrointestinal variables. Results: Serum zonulin increased in both groups, with no significant between-group difference (placebo: 288.2 to 425.3 ng/mL; probiotic: 239.5 to 453.7 ng/mL; p = 0.882; ANCOVA p = 0.463). Pre-dialysis urea decreased within the probiotic group, but the between-group difference was not significant (p = 0.305). Serum phosphorus showed a greater reduction in the probiotic group than in the placebo group (p = 0.011; ANCOVA p = 0.011). No significant differences were observed for anthropometric or hemodynamic outcomes. Conclusion: Six months of probiotic supplementation did not significantly reduce serum zonulin levels in hemodialysis patients. Although a favorable effect on serum phosphoruswas observed, these findings do not support a measurable impact of this probiotic regimen on serum zonulin and highlight the need for larger studies incorporating direct assessments of intestinal permeability and gut microbiota.