Effects of probiotic and synbiotic supplementation on fibrinogen and plasminogen activator inhibitor-1 concentrations: A Grading of Recommendations Assessment, Development and Evaluation-based systematic review and meta-analysis.

ObjectiveElevated fibrinogen and plasminogen activator inhibitor-1 concentrations are associated with impaired fibrinolysis and increased cardiovascular and thrombotic risk. Although probiotic and synbiotic supplementation may influence inflammatory and hemostatic pathways, their effects on these biomarkers remain uncertain. This systematic review and meta-analysis of randomized controlled trials evaluated the effects of probiotic and synbiotic supplementation on plasma concentrations of fibrinogen and plasminogen activator inhibitor-1.MethodsThis systematic review and meta-analysis included randomized controlled trials conducted in adults, irrespective of health status. PubMed, Scopus, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through June 2025. Trials comparing oral probiotic or synbiotic supplementation with placebo or no intervention and reporting fibrinogen or plasminogen activator inhibitor-1 concentrations were included. Pooled estimates with 95% confidence intervals were calculated using the Hartung-Knapp-Sidik-Jonkman random-effects model. Heterogeneity was assessed using I2, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation. The review was not prospectively registered; following completion of the review, it was retrospectively registered with the Open Science Framework on 5 September 2026 (Registration DOI: 10.17605/OSF.IO/R3Y82).ResultsFifteen randomized controlled trials involving 892 participants were included. Probiotic or synbiotic supplementation did not significantly reduce fibrinogen (mean difference = -0.15, 95% confidence interval: -0.48 to 0.18; p = 0.34) or plasminogen activator inhibitor-1 concentrations (mean difference = -0.47, 95% confidence interval: -1.58 to 0.65; p = 0.33). Subgroup analyses and meta-regression did not reveal significant effect modification. The certainty of the evidence was low because of inconsistency and imprecision.ConclusionWe found no significant reduction in fibrinogen or plasminogen activator inhibitor-1 concentrations with probiotic or synbiotic supplementation. Given the low certainty of evidence and heterogeneity across trials, further high-quality randomized controlled trials are needed to identify whether specific formulations or patient groups are associated with improvements in these hemostatic and fibrinolytic biomarkers.