S2381 The Impact of Gut Microbiota Modulation on NAFLD Progression: A Systematic Review and Meta-Analysis From Human Trials

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern with limited treatment options. Gut microbiota dysbiosis has been implicated in the pathogenesis of NAFLD. This systematic review and meta-analysis aimed to evaluate the effects of gut microbiota modulation strategies, including administration of probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation (FMT), or farnesoid X receptor (FXR) agonists, on the progression of NAFLD. Methods: We included randomized controlled trials and prospective cohort studies involving adults and children with NAFLD/NASH who received probiotics, prebiotics, synbiotics, antibiotics, FMT, or farnesoid X receptor (FXR) agonists, compared to placebo or standard care. PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov were searched until March 15, 2025. Risk of bias was assessed using the Cochrane RoB 2.0 tool. A random-effects model synthesized continuous outcomes as mean differences (MD) with 95% confidence intervals (CI). Results: Forty studies involving 3,415 participants were included. Probiotics/prebiotics/synbiotics, antibiotics, FMT, and FXR agonists significantly improved liver enzymes (alanine aminotransferase MD: -11.49 U/L, 95% CI: -14.69 to -8.30; AST MD: -5.95 U/L, 95% CI: -6.52 to 5.38). Gut microbial diversity also improved. Heterogeneity was moderate to high across outcomes. The risk of bias was low, although some concerns were noted in most studies. Adverse events were mild and infrequent across interventions. Conclusion: This systematic review and meta-analysis demonstrate that gut microbiota modulation strategies—including probiotics, prebiotics, synbiotics, antibiotics, FMT, and FXR agonists—improve liver enzymes, metabolic markers, and inflammation in NAFLD patients, with FXR agonists showing the greatest benefit. Sensitivity analysis confirmed these results, though limitations such as small sample sizes, short durations, and inconsistent data reporting were noted. Despite potential bias from language restrictions and reviewer limitations, the findings support incorporating microbiota-targeted strategies into NAFLD management, with probiotics and synbiotics offering safe adjunctive options and FXR agonists showing promise with careful monitoring. Future large-scale, long-term trials with standardized outcomes are needed to confirm efficacy and identify patient subgroups most likely to benefit.