Mohammad Vesal Bideshki
1,2 
, Naimeh Mesri Alamdari
3 , Hossein Bahari
4 , Zahra Asadi
5 , Behrad Sadeghi
6 , Tohid Salehi
7 , Hannane Jozi
7 , Mehrdad Behzadi
5,8 , Seyed Fazel Zinat Motlagh
9, Zahra Sohrabi
10,8* , Ali Rashidinejad
11* 1 Bio Environmental Health Hazards Research Center, Jiroft University of Medical Sciences, Jiroft, Iran
2 Clinical Research Development Unit, Imam Khomeini Hospital, Jiroft University of Medical Sciences, Jiroft, Iran
3 Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 Transplant Research Center, Clinical Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
5 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
6 Department of Agricultural, Forest and Food Science (DISAFA), University of Torino, Grugliasco, Torino 10095, Italy
7 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
8 Department of Community Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
9 Social Determinants of Health Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
10 Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
11 Riddet Institute, Massey University, Private Bag 11222, Palmerston North, New Zealand
Abstract
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.