Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects nearly one-third of the adult population worldwide, and currently, there are no approved pharmacological therapies. Akkermansia muciniphila, a bacterium found in the gut, has been identified as a promising therapeutic candidate due to its influence on the gut-liver axis. OBJECTIVE: This systematic review aims to evaluate the efficacy of A. muciniphila in preclinical mouse models of NAFLD, focusing on its effects on body weight, glucolipid metabolism, liver function, gut barrier integrity, gut microbiota composition, inflammation, and immune response. METHODS: Following PRISMA 2020 guidelines, a comprehensive search was conducted in PubMed, Scopus, Web of Science, and Google Scholar until September 30, 2025, for studies investigating A. muciniphila interventions in NAFLD mouse models. Inclusion criteria comprised mouse models of NAFLD, MAFLD, or NASH that involved A. muciniphila administration alongside a control group. Data were extracted concerning study characteristics, intervention details, and outcomes. The quality assessment of the studies was performed using the SYRCLE's Risk of Bias tool. RESULTS: Thirteen studies were included, predominantly employing C57BL/6 mice and high-fat diets. Results indicated that A. muciniphila reduced body weight, hepatic steatosis, and serum lipid levels, while improving insulin sensitivity and decreasing liver enzyme levels (ALT, AST). It also enhanced gut barrier function by upregulating tight junction protein expression and reducing lipopolysaccharide (LPS) translocation. Furthermore, anti-inflammatory effects were evidenced by decreased levels of TNF-α, IL-6, and MCP-1, alongside immunomodulation through the balance of Th17 and Treg cells. CONCLUSION: A. muciniphila exhibits potential in the management of preclinical NAFLD by improving metabolic, hepatic, and gut-related parameters. However, the absence of clinical trials limits the translatability of these findings. Future clinical investigations are imperative to establish efficacy, optimize dosing, and evaluate long-term safety. TRIAL REGISTRATION: This systematic review has been documented with PROSPERO under the identifier: CRD42024610627.