Effects of synbiotic supplementation on oxidative stress biomarkers in adults: an updated GRADE-assessed systematic review and meta-analysis of randomized controlled trials

Synbiotics (combined probiotics + prebiotics) may ameliorate oxidative stress via gut microbiota–mediated mechanisms. However, previous syntheses were limited in biomarker scope and contaminated by retracted or compromised trials. This updated meta-analysis of randomized controlled trials (RCTs) aims to quantify the effects of synbiotic supplementation on a comprehensive panel of oxidative stress biomarkers in adults and to appraise the certainty of evidence. Following PRISMA guidance and a registered protocol, RCTs in adults comparing oral synbiotic supplementation (≥ 3 weeks) versus placebo were eligible. Primary outcomes were changes in malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), nitric oxide (NO), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione (GSH). Data were pooled using a random-effect model (standardized mean differences, SMD; 95% CI). Heterogeneity (I²), sensitivity, subgroup and publication-bias analyses were performed. Evidence certainty was rated with GRADE; studies formally retracted or with serious concerns were excluded. Eighteen RCTs were included. Synbiotic supplementation significantly reduced MDA (SMD: -0.87; 95% CI: -1.37, -0.37), TOS (SMD: -0.55; 95% CI: -1.03, -0.08) and OSI (SMD: -0.46; 95% CI: -0.78, -0.15). Antioxidant markers, including TAC (SMD: 0.25; 95% CI: 0.06, 0.43), SOD (SMD: 0.57; 95% CI: 0.13, 1.00), GSH (SMD: 0.70; 95% CI: 0.11, 1.28), and GPx (SMD: 1.40; 95% CI: 0.39, 2.40), were increased. GRADE ratings ranged from very low (MDA, GPx) to moderate (OSI). Synbiotic supplementation may improve certain oxidative stress biomarkers, including TAC, GSH, and MDA. However, findings for NO and OSI should be interpreted with caution due to the limited number of available studies and the low to very low certainty of evidence for some outcomes according to GRADE criteria. Further high-quality, large-scale RCTs are warranted to confirm these effects. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251103060 .