Modulating the Gut-Liver Axis: Anti-Inflammatory Mechanisms of Probiotics and Prebiotics in MASLD

Non-alcoholic fatty liver disease (NAFLD), recently reclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), is a prevalent metabolic disorder with significant inflammatory underpinnings. Emerging evidence underscores the gut-liver axis as a pivotal pathway in MASLD pathogenesis through which dysbiosis drives cytokine-mediated inflammation, fibrosis, and disease progression. This review synthesizes preclinical and clinical findings on how probiotics and prebiotics modulate key inflammatory cytokines-including TNF-α, IL-6, IL-1β, IL-10, IL-17, and TGF-β-to ameliorate MASLD. The literature demonstrates that these interventions converge on the TLR4/NF-κB axis as the central mechanistic driver of cytokine dysregulation in MASLD. By restoring gut barrier integrity and reducing endotoxin (LPS) translocation, probiotics and prebiotics suppress TLR4/NF-κB activation, which secondarily inhibits the NLRP3 inflammasome (reducing IL-1β/IL-18), downregulates pro-inflammatory cytokines (TNF-α, IL-6, IL-17), and enhances anti-inflammatory signals (IL-10) through crosstalk with PPAR-α, AMPK, and Nrf2 pathways. In animal models, probiotic strains such as Bifidobacterium, Lactobacillus, and Akkermansia muciniphila consistently downregulate pro-inflammatory cytokines and enhance anti-inflammatory signals. The same is true for prebiotics, including inulin, oat β-glucan, and synbiotic formulations. However, clinical trial outcomes remain heterogeneous, influenced by strain specificity, intervention duration, and patient heterogeneity. Collectively, this review highlights the therapeutic potential of microbiota-targeted interventions to rebalance cytokine networks and proposes future directions for personalized, mechanism-driven approaches to the management of MASLD.