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Context Nonalcoholic fatty liver disease (NAFLD) is considered the leading cause of chronic liver disease worldwide. To date, no confirmed medication is available for the treatment of NAFLD. Previous studies showed the promising effects of gut microbiome–targeted therapies; however, the results were controversial and the strength of the evidence and their clinical significance remained unclear. Objectives This umbrella study summarizes the results of meta-analyses investigating the effects of probiotics, prebiotics, and synbiotics on liver enzymes in the NAFLD population. Data Source A comprehensive search of the PubMed, Scopus, Web of Science, and Cochrane Library databases was done up to December 20, 2022, to find meta-analyses on randomized control trials reporting the effects of gut microbial therapy on patients with NAFLD. Data Extraction Two independent investigators extracted data on the characteristics of meta-analyses, and any discrepancies were resolved by a third researcher. The AMSTAR2 checklist was used for evaluating the quality of studies. Data Analysis A final total of 15 studies were included in the analysis. Results showed that microbiome-targeted therapies could significantly reduce levels of alanine aminotransferase (ALT; effect size [ES], −10.21; 95% confidence interval [CI], −13.29, −7.14; P < 0.001), aspartate aminotransferase (AST; ES, −8.86; 95%CI, −11.39, −6.32; P < 0.001), and γ-glutamyltransferase (ES, −5.56; 95%CI, −7.92, −3.31; P < 0.001) in patients with NAFLD. Results of subgroup analysis based on intervention showed probiotics could significantly reduce levels of AST (ES, −8.69; 95%CI, −11.01, −6.37; P < 0.001) and ALT (ES, −9.82; 95%CI, −11.59, −8.05; P < 0.001). Synbiotics could significantly reduce levels of AST (ES, −11.40; 95%CI, −13.91, −8.88; P < 0.001) and ALT (ES, −11.87; 95%CI, −13.80, −9.95; P < 0.001). Prebiotics had no significant effects on AST and ALT levels (ES, −2.96; 95%CI, −8.12, 2.18, P = 0.259; and ES, −4.69; 95%CI, −13.53, 4.15, P = 0.299, respectively). Conclusion Gut microbiome–targeted therapies could be a promising therapeutic approach in the improvement of hepatic damage in patients with NAFLD. However, more studies are needed to better determine the best bacterial strains, duration of treatment, and optimum dosage of gut microbiome–targeted therapies in the treatment of the NAFLD population. Systematic Review Registration PROSPERO registration no. CRD42022346998. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is a global health challenge, with a rising rate in line with other metabolic diseases. We aimed to assess the global prevalence of NAFLD in adult and pediatric populations., Methods: PubMed, Scopus and Web of Science databases were systematically searched up to May 2023. Heterogeneity was assessed using Cochran's Q test and I 2 statistics, and random-effects model was used for meta-analysis. Analyses were performed using STATA version 18., Results: A total of 479 studies with 78,001,755 participants from 38 countries were finally included. The global prevalence of NAFLD was estimated to be 30.2% (95% CI: 28.7-31.7%). Regionally, the prevalence of NAFLD was as follows: Asia 30.9% (95% CI: 29.2-32.6%), Australia 16.1% (95% CI: 9.0-24.8%), Europe 30.2% (95% CI: 25.6-35.0%), North America 29% (95% CI: 25.8-32.3%), and South America 34% (95% CI: 16.9-53.5%). Countries with a higher human development index (HDI) had significantly lower prevalence of NAFLD (coefficient = -0.523, p = 0.005). Globally, the prevalence of NAFLD in men and women was 36.6% (95% CI: 34.7-38.4%) and 25.5% (95% CI: 23.9-27.1%), respectively. The prevalence of NAFLD in adults, adults with obesity, children, and children with obesity was 30.2% (95% CI: 28.8-31.7%), 57.5% (95% CI: 43.6-70.9%), 14.3% (95% CI: 10.3-18.8%), and 38.0% (95% CI: 31.5-44.7%), respectively., Conclusion: The prevalence of NAFLD is remarkably high, particularly in countries with lower HDI. This substantial prevalence in both adults and children underscores the need for disease management protocols to reduce the burden., Competing Interests: Conflict of Interest The authors declare that they have no competing interests., (Copyright © 2024 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)