Prebiotic Supplementation in Celiac Disease: A Systematic Review of Clinical Efficacy, Safety, and Nutritional Outcomes.

BACKGROUND AND AIMS: Despite a strict gluten-free diet (GFD), many patients with celiac disease (CD) continue to experience symptoms and nutrient deficiencies. Prebiotics, non-digestible substrates that foster beneficial bacteria and short-chain fatty acid (SCFA) production, may offer adjunctive benefits, though their role in CD remains unclear. We aimed to determine the clinical efficacy, safety, and nutritional outcomes of prebiotics in CD. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Embase, Web of Science, and CENTRAL through May 2025 for clinical studies evaluating the effects of prebiotics in CD, derived from either supplements or foods naturally abundant in prebiotics. Eligible trials and observational studies were assessed using Cochrane RoB 2.0 or Newcastle-Ottawa tools, and data were synthesized narratively. RESULTS: Twelve studies (1,066 participants) were included. Oligofructose-enriched inulin (Synergy 1) increased fecal SCFAs by 31%, Bifidobacterium abundance, osteocalcin, and serum vitamins D and E. It also reduced hepcidin by 61% without gastrointestinal intolerance. Oats (50-70 g/day) for up to 24 months maintained histologic remission, negative serology, and improved dietary iron, fiber, thiamin, and zinc intake without worsening hemoglobin or ferritin status. Quinoa modestly lowered cholesterol, and amaranth enhanced growth and corrected trace element deficiencies in children. No study reported serious adverse events; adherence improved when prebiotics diversified the GFD. CONCLUSIONS: Prebiotics appear safe and may enhance microbiota composition, nutrient absorption, and barrier integrity without compromising mucosal healing. Larger standardized randomized trials are needed to confirm these findings.