Decoding dysbiosis: the role of gut microbiota in MASLD progression and emerging therapeutic interventions

Metabolic dysfunction-associated steatotic liver disease (MASLD), affects a substantial proportion of the global population and is closely associated with metabolic disorders. The gut microbiota, comprising a diverse community of microorganisms within the gastrointestinal tract, plays a crucial role in maintaining host health. Dysbiosis, defined as an imbalance in this microbial ecosystem, has been increasingly implicated in the development and progression of liver diseases, including MASLD. This review examines the role of the gut microbiota in MASLD pathogenesis and highlights its potential as a therapeutic target. The gut-liver axis facilitates bidirectional communication between the intestine and the liver, thereby influencing metabolic regulation. In MASLD, dysbiosis characterized by reduced microbial diversity and an increased abundance of Gram-negative bacteria leads to altered bile acid metabolism, increased intestinal permeability, enhanced endotoxin translocation, and hepatic inflammation. Additionally, it disrupts short-chain fatty acid production and interferes with the endocannabinoid system and choline metabolism, collectively driving disease progression. Emerging non-invasive diagnostic approaches, including gut microbiome profiling, show promise for early detection. Although specific pharmacological treatments remain limited, microbiota-targeted strategies such as probiotics, prebiotics, and synbiotics aim to restore microbial balance. Furthermore, emerging modalities within microbiome-based therapies, including mesenchymal stromal cell therapy and bacteriophage therapy, offer potential for targeted modulation of the gut microbiota and liver repair. The gut microbiota-liver axis plays a central role in the pathogenesis of MASLD. Growing insights into this relationship have driven the development of microbiome-based diagnostic and therapeutic approaches. Non-invasive diagnostic tools, particularly gut microbiome profiling, show promise for early detection. Therapeutically, microbiota-targeted strategies including probiotics, prebiotics, synbiotics, and emerging modalities such as cellular and bacteriophage-based therapies offer potential to restore microbial balance and improve liver function. Nevertheless, robust clinical studies are essential to validate their efficacy, safety, and applicability in personalized MASLD management.