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Effects of Probiotics on Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. OBJECTIVES: Several studies have suggested that the gut-liver axis is closely related to non-alcoholic fatty liver disease (NAFLD). However, the application of probiotic therapies for NAFLD has not undergone a systematic and comprehensive assessment of the described effects. Therefore, this study was designed to conduct a meta-analysis based on a randomized controlled trial (RCT) to systematically evaluate the efficacy of probiotics in the treatment of NAFLD. METHODS: This study carried out a literature search of published scientific data (up to April 2021) on probiotic therapies of NAFLD. This was performed from five electronic reference databases including PubMed, Medline, Embase, Web of Science and Cochrane library. All the relevant randomized clinically controlled trials of probiotics in the treatment of NAFLD were included according to specified eligibility criteria. The quality of the included literature was evaluated, and the corresponding data were extracted using the RevMan5.4 software. RESULTS: : A total of 9 randomized clinical trials involving 352 patients with NAFLD were included in this study. The patients were proven eligible through a set of inclusion/exclusion criteria. Results of the meta-analysis study showed that probiotic therapy group have significant reduction in the levels of serum indices: alanine aminotransferase (ALT) (WMD: -8.64, 95% CI: [-10.74, -6.54], P<0.00001), aspartate transaminase (AST) (WMD: -6.94, 95% CI: [-8.8, -5.08], P<0.00001) and total cholesterol (TC) (WMD: -13.49, 95% CI: [-23.42, -3.56], P=0.008) in comparison with the control group. Probiotic therapy was not associated with changes in body mass index (BMI) (WMD =-0.68, 95% CI: -1.97-0.60, P=0.30), homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: -0.31, 95% CI: [-0.36, 0.98], P=0.36) and tumor necrosis factor (TNF) (WMD: -3.27, 95% CI: [-9.55, 3.02], P=0.31). Subgroup analyses of BMI indicated that three or more composite probiotics or probiotic treatment for more than three months can significantly reduce the BMI level. CONCLUSION: : This systematic review and meta-analysis demonstrated that modulating gut microbiota may be utilized as an effective method to improve liver function and reduce blood lipid levels in patients with NAFLD.