Effects of probiotics and synbiotics on liver enzymes, glucose and lipid metabolism, and inflammatory markers in patients with metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis.

OBJECTIVE: The potential of probiotics and synbiotics as a targeted microbiome intervention for metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD) has garnered significant attention; however, their clinical efficacy exhibits substantial heterogeneity. This study aimed to systematically evaluate the clinical efficacy of adjunctive probiotic and synbiotic therapy in MASLD/NAFLD and explore the sources of this heterogeneity. METHODS: A systematic search was conducted across PubMed, Web of Science, Embase, and The Cochrane Library for randomized controlled trials (RCTs) published up to June 2026. RevMan 5.3 and Stata 17.0 were utilized to pool effect sizes [mean difference (MD)/standardized mean difference (SMD)]. Subgroup analyses and the GRADE system were employed to investigate heterogeneity and assess the quality of evidence. RESULTS: A total of 30 RCT publications encompassing 1,516 unique patients were included. The meta-analysis demonstrated that probiotics and synbiotics significantly mitigated liver injury (ALT, AST) and systemic inflammation (TNF-α), while improving specific metabolic parameters (FPG, TC, HDL-C) (p < 0.05). Although the overall effects on triglycerides (TG) and insulin resistance (HOMA-IR) were not statistically significant, subgroup analyses revealed more pronounced benefits in glucolipid metabolism among younger populations (<50 years), Asian cohorts, and those receiving short-to-medium-term interventions (<24 weeks). Furthermore, insulin resistance was significantly ameliorated in non-diabetic MASLD/NAFLD patients. CONCLUSION: As an adjunct to lifestyle interventions, probiotics and synbiotics effectively ameliorate liver injury and systemic inflammation in patients with MASLD/NAFLD. Their regulatory efficacy on lipid metabolism and insulin resistance is significantly influenced by variables including patient age, geographical region, and intervention duration. For younger, non-diabetic MASLD/NAFLD patients, short-to-medium-term probiotic interventions (<24 weeks) yield optimal metabolic benefits. These findings underscore the necessity of adopting precision microbiome-targeted intervention strategies based on patient stratification in future clinical practice. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261442665, identifier PROSPERO (CRD420261442665).