Use of probiotics, prebiotics, and synbiotics in non-alcoholic fatty liver disease: A systematic review and meta-analysis

Background and aim: Patients with non-alcoholic fatty liver disease (NAFLD) exhibit compositional changes in their gut microbiome, which represents a potential therapeutic target. Probiotics, prebiotics, and synbiotics are microbiome-targeted therapies that have been proposed as treatment for NAFLD. We aim to systematically review the effects of these therapies in liver-related outcomes of NAFLD patients.

Methods: We conducted a systematic search in Embase (Ovid), Medline (Ovid), Scopus, Cochrane, and EBSCOhost from inception to August 19, 2022. We included randomized controlled trials (RCTs) that treated NAFLD patients with prebiotics and/or probiotics. We meta-analyzed the outcomes using standardized mean difference (SMD) and assessed study heterogeneity using Cochran's Q test and I² statistics. Risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool.

Results: A total of 41 (18 probiotics, 17 synbiotics, and 6 prebiotics) RCTs were included. Pooled data demonstrated that the intervention had significantly improved liver steatosis (measured by ultrasound grading) (SMD: 4.87; 95% confidence interval [CI]: 3.27, 7.25), fibrosis (SMD: -0.61 kPa; 95% CI: -1.12, -0.09 kPa), and liver enzymes including alanine transaminase (SMD: -0.86 U/L; 95% CI: -1.16, -0.56 U/L), aspartate transaminase (SMD: -0.87 U/L; 95% CI: -1.22, -0.52 U/L), and gamma-glutamyl transferase (SMD: -0.77 U/L; 95% CI: -1.26, -0.29 U/L).

Conclusions: Microbiome-targeted therapies were associated with significant improvements in liver-related outcomes in NAFLD patients. Nevertheless, limitations in existing literature like heterogeneity in probiotic strains, dosage, and formulation undermine our findings. This study was registered with PROSPERO (CRD42022354562) and supported by the Nanyang Technological University Start-up Grant and Wang Lee Wah Memorial Fund.