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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: Smoking poses a significant risk for colorectal cancer (CRC), considered the third leading reason for cancer-related deaths worldwide. However, there has been limited research on the relationship between smoking and CRC in the Eastern Mediterranean Regional Office (EMRO). Therefore, a meta-analysis was conducted to combine available data and gain a comprehensive understanding of the relationship between smoking and CRC in EMRO. Methods: Two independent researchers searched PubMed, Scopus, and Web of Science until December 2022. The included studies were checked for risk of bias administering the Newcastle-Ottawa scale. Heterogeneity was evaluated using I2 statistics and the Cochrane test. Publication bias was determined through funnel plot analysis and Egger's regression test. Additionally, a meta-regression analysis explored the impact of a country's Human Development Index (HDI) on the relationship between smoking and CRC. Results: The final analysis included 26 studies, revealing a significant association between smoking and CRC (OR = 1.40; 95% CI: 1.11 - 1.78; P = 0.004). Moreover, smoking had a more pronounced adverse effect on CRC in countries with higher HDIs compared to those with lower HDIs (OR = 1.30; 95% CI: 0.99 - 1.71; P = 0.054). Conclusions: Our findings underscore the importance of implementing smoking cessation programs and policies in EMRO countries, as they demonstrate a positive relationship between smoking and the risk of CRC. Furthermore, the results suggest that a country's level of human development may influence the association between smoking and CRC. Further research is needed to investigate this potential connection and develop targeted public health interventions. [ABSTRACT FROM AUTHOR]