Tabriz University of Medical Sciences BioImpacts 2228-5652 16 1 2026 01 04 Effects of synbiotic supplementation on inflammatory and anti-inflammatory markers in adults: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials 32952 32952 10.34172/bi.32952 EN Mohammad Vesal Bideshki https://orcid.org/0000-0002-5098-6547 Naimeh Mesri Alamdari https://orcid.org/0000-0003-2563-8193 Hossein Bahari https://orcid.org/0000-0002-3787-2713 Zahra Asadi https://orcid.org/0000-0003-2412-1782 Behrad Sadeghi https://orcid.org/0009-0009-6800-9216 Tohid Salehi https://orcid.org/0009-0001-2595-8392 Hannane Jozi https://orcid.org/0000-0003-4314-1084 Mehrdad Behzadi https://orcid.org/0000-0002-2029-5008 Seyed Fazel Zinat Motlagh Zahra Sohrabi https://orcid.org/0000-0003-4572-3942 Ali Rashidinejad https://orcid.org/0000-0002-5664-170X Journal Article 10.34172/bi.32952 2025 10 11 2026 07 08 Introduction: Systemic inflammation contributes to chronic diseases, and synbiotics may modulate these pathways via gut microbiota. This systematic review and meta-analysis evaluates synbiotic supplementation effects on adult inflammatory and anti-inflammatory markers. Methods: A comprehensive search of PubMed/MEDLINE, Web of Science, Scopus, Embase, and CENTRAL, supplemented by Google Scholar and manual reference-list searches, identified 63 randomized controlled trials involving 3,725 participants. Eligible studies administered synbiotics for at least 3 weeks. Data were pooled using random-effects models to calculate standardized mean differences (SMDs). Risk of bias was assessed using the Cochrane risk-of-bias tool, and the certainty of evidence was evaluated using the GRADE approach. Results: Synbiotic supplementation was associated with a reduction in C-reactive protein (CRP) (SMD: -0.49, 95% CI: -0.67 to -0.31), interleukin-6 (IL-6) (SMD: -0.33, 95% CI: -0.61 to -0.05), IL-8 (SMD: -0.62, 95% CI: -1.15 to -0.09), and tumor necrosis factor-α (TNF-α) (SMD: -0.38, 95% CI: -0.65 to -0.11). Conversely, anti-inflammatory IL-10 significantly increased (SMD: 0.30, 95% CI: 0.002 to 0.59). No significant changes occurred in IL-1β, IFN-γ, lipopolysaccharide (LPS), or adiponectin. Publication bias was detected for CRP, and evidence certainty ranged from very low to low. Conclusion: Synbiotic appears to modulate inflammatory status by reducing key pro-inflammatory biomarkers (CRP, IL-6, IL-8, and TNF-α), and increasing the anti-inflammatory cytokine IL-10. Nevertheless, the strength of these conclusions is limited by the low to very low certainty of the available evidence, as well as potential publication bias affecting the CRP estimate. Future standardized, adequately powered RCTs are required to validate these clinical findings.