The Efficacy of Gut Microbiome-Modulating Therapies on Liver Cirrhosis: A Systematic Review and Network Meta-Analysis

Objective: Gut microbiome-modulating therapies are potential strategies for managing liver cirrhosis (LC), yet head-to-head comparisons to determine the optimal intervention are lacking. This study aimed to evaluate and rank the therapeutic efficacy of these therapies on liver function and disease progression in patients with LC. Methods: We searched major databases (PubMed, Web of Science, Embase, Cochrane Library) for randomized controlled trials (RCTs) published from January 1, 2000, to December 30, 2024. Interventions included probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) versus placebo or standard care. Primary outcomes were hepatic function indicators; secondary outcomes included inflammatory markers. Data were analyzed using random-effects frequentist network meta-analyses. The study was registered on PROSPERO (CRD420251000506). Results: Seventeen studies comprising 1051 individuals were included. Synbiotics demonstrated the most significant efficacy among all interventions, showing superior reduction in blood ammonia levels compared to placebo (Mean Difference (MD): -5.57), probiotics, and prebiotics. Prebiotics showed significant differences in lowering endotoxin levels compared to placebo (MD: -3.29) and probiotics. Furthermore, relative to placebo, prebiotics significantly reduced tumor necrosis factor-alpha (MD: -2.30) and interleukin-6 levels (MD: -4.60). Conclusions: This network meta-analysis advances current knowledge by establishing an evidence-based hierarchy of efficacy. Synbiotics are most effective for reducing blood ammonia, whereas prebiotics demonstrate superior efficacy in lowering endotoxin and inflammatory markers. These results support a personalized therapeutic approach: prioritizing synbiotics for patients with hyperammonemia, and prebiotics for those characterized by systemic inflammation. Future high-quality RCTs are needed to standardize specific strain combinations.