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Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
Metabolic Dysfunction-Associated Steatotic Liver Disease: An Update Narrative Review of the Therapeutic Potential of
Syifa Mustika1, Sri Utami2, Nur Estu Wijayanti Saputri2
1Gastroenterohepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang 65111, Indonesia.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced older exclusion-based terminology as the preferred term for steatotic liver disease associated with cardiometabolic risk factors. MASLD is now among the most common causes of chronic liver disease and may progress from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. This updated rigorous narrative review synthesizes current evidence on MASLD diagnosis and management, with emphasis on the gut-liver axis and the therapeutic potential of combining probiotics with metformin. A structured narrative search was conducted in PubMed, PMC, ScienceDirect, Taylor & Francis, Cochrane Library, and Google Scholar using the keywords "MASLD", "MAFLD", "NAFLD", "MASH", "probiotics", "synbiotics", "metformin", and "gut-liver axis". The review was designed as a narrative synthesis rather than a systematic review. Current guidance supports stepwise risk stratification using serum fibrosis scores followed by elastography or advanced imaging when indicated. Ultrasonography remains accessible but has limited sensitivity for mild steatosis, is operator-dependent, and is not sufficient for comprehensive assessment of fibrosis or disease activity. Metformin is appropriate for type 2 diabetes mellitus and improves insulin resistance, but current guidelines do not recommend it as a targeted treatment for MASH because histological benefit has not been consistently demonstrated. Probiotics and synbiotics may improve aminotransferases, inflammatory markers, lipid parameters, intestinal barrier function, and gut dysbiosis; however, findings vary by strain, formulation, dose, treatment duration, population, and endpoint. The combination of probiotics and metformin is mechanistically plausible because it targets both metabolic dysfunction and intestinal dysbiosis, but human evidence remains limited. Larger, strain-specific, adequately powered trials using standardized MASLD criteria and clinically meaningful endpoints are required before routine clinical recommendations.
Insights
Metabolic dysfunction-associated steatotic liver disease (MASLD) is common and can progress. Combining probiotics and metformin shows promise for MASLD management by targeting metabolic issues and gut dysbiosis, but more research is needed.
Area of Science:
- Hepatology
- Gastroenterology
- Metabolic Diseases
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition linked to cardiometabolic risk factors.
- MASLD can advance to severe liver conditions, including MASH, fibrosis, cirrhosis, and hepatocellular carcinoma.
- Understanding the gut-liver axis is crucial for managing MASLD.
Purpose of the Study:
- To review current evidence on MASLD diagnosis and management.
- To explore the therapeutic potential of combining probiotics with metformin.
- To emphasize the role of the gut-liver axis in MASLD.
Main Methods:
- A structured narrative literature search was performed across major scientific databases.
- Keywords included MASLD, MASH, probiotics, metformin, and gut-liver axis.
- The study employed a narrative synthesis approach.
Main Results:
- Current MASLD diagnosis relies on risk stratification and advanced imaging.
- Metformin is recommended for type 2 diabetes but not specifically for MASH.
- Probiotics/synbiotics may improve liver markers and gut health, but results vary.
- The combination of probiotics and metformin is mechanistically sound but lacks robust human data.
Conclusions:
- Further large-scale, strain-specific trials are necessary to establish the efficacy of probiotics and metformin combinations for MASLD.
- Standardized MASLD criteria and clinically meaningful endpoints are needed for future research.
- Targeting the gut-liver axis presents a promising avenue for MASLD therapeutics.
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