Anti-inflammatory Effects of Probiotics and Synbiotics on Patients with Non-Alcoholic Fatty Liver Disease: an Umbrella Study on Meta-Analyses

Background and aim: The impact of chronic low-grade inflammation in the development of nonalcoholic fatty liver disease (NAFLD) has been studied widely. Previous studies showed gut pathogens ' effects on inflammation development in NAFLD patients; hence, hypothetically, gut microbial therapy by administration of probiotics, synbiotics, and prebiotics may alleviate inflammation in these individuals. Several studies were performed in this regard; however, conflicting results were obtained. In this study, we aimed to comprehensively evaluate the effects of gut microbial therapy on inflammatory markers in NAFLD patients in a meta-umbrella design. Methods: Two independent researchers investigated international databases, including PubMed, Web of Science, Scopus, and Cochrane Library, from inception until March 2023. Meta-analyses evaluating the impact of probiotics, synbiotics, or prebiotics on inflammatory markers of patients with NAFLD were eligible for our study. AMASTAR 2 checklist was used to evaluate the quality of included studies. Random effect model was performed for the analysis, and Egger ' s regression test was conducted to determine publication bias. Results: A total number of 12 studies were entered into our analysis. Our findings revealed that gut microbial therapy could significantly reduce serum C-reactive protein (CRP) levels among NAFLD patients (ES: -0.58; 95% CI: -0.73, -0.44, P < 0.001). In subgroup analysis, this reduction was observed with both probiotics (ES: -0.63; 95% CI: -0.81, -0.45, P < 0.001) and synbiotics (ES: -0.49; 95% CI: -0.74, -0.24, P < 0.001). In addition, gut microbial therapy could significantly decrease tumor necrosis factor-a (TNF-a) levels in NAFLD patients (ES: -0.48; 95% CI: -0.67 to -0.30, P < 0.001). In subgroup analysis, this decrease was observed with probiotics (ES: -0.32; 95% CI: -0.53, -0.11, P = 0.002) and synbiotics (ES: -0.96; 95% CI: - 1.32, -0.60, P < 0.001). Not enough information was available for assessing prebiotics' impacts. Conclusion: The results of this umbrella review suggest that probiotics and synbiotics have promising effects on inflammatory markers, including TNF-a and CRP; however, more research is needed regarding the effects of prebiotics. PROSPERO registration code: CRD42022346998. (c) 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.