S376 Effect of Fecal Microbiota Transplantation on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a prevalent liver condition closely linked to obesity, insulin resistance, and gut microbiota dysbiosis. Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy to modulate the gut-liver axis. This systematic review evaluated clinical trial evidence on the efficacy of FMT in improving hepatic and metabolic outcomes in MASLD. Methods: A systematic search of PubMed, Scopus, and Web of Science from 2010 to April 2025 identified randomized controlled trials (RCTs) assessing FMT in adult MASLD patients. Eligible studies included those with clinical, biochemical, histologic, or imaging-based liver outcomes. One preclinical mouse study was also summarized narratively for biological insight. Data extraction and risk-of-bias assessment were performed independently by 2 reviewers using the Cochrane RoB 2.0 tool. Results: Three RCTs (n = 82) were included. One study (n = 36) demonstrated significant hepatic fat reduction in lean MASLD patients receiving FMT (CAP: −42.1 dB/m, P < 0.05) and ALT improvement (−12.6 U/L), alongside improved microbial diversity. Another trial (n = 21) showed downregulation of hepatic inflammatory gene expression (e.g., IL-1β, P < 0.05) and beneficial metabolomic shifts post-allogenic FMT. A third RCT (n = 25) reported no change in HOMA-IR or MRI-PDFF overall, but improved intestinal permeability in a subset (lactulose:mannitol ratio: 0.038 to 0.021, P = 0.03). An animal study supported these findings with reduced NAS scores (5.3 to 2.1, P < 0.01) and enhanced gut barrier integrity. Overall, FMT showed modest but promising effects, particularly in metabolically distinct NAFLD phenotypes. Conclusion: FMT appears to beneficially modulate gut microbiota and improve selected hepatic and metabolic parameters in MASLD, particularly in metabolically distinct subgroups. However, findings remain preliminary due to limited sample sizes and outcome heterogeneity. Larger, standardized trials are needed to clarify therapeutic efficacy and identify optimal donor characteristics and patient phenotypes.