Gut-liver axis drives the triple mechanism of liver inflammation-carcinogenesis: Microbial-immune-metabolic network

The gut-liver axis, through intricate microbial-immune-metabolic networks, plays a pivotal role in driving hepatic fibrosis. Chronic liver injury activates hepatic stellate cells, resulting in pathological extracellular matrix deposition. Gut dysbiosis, characterized by altered microbial metabolites and bacterial translocation, significantly modulates this process. Bile acid and short-chain fatty acid metabolism, alongside immune responses involving Toll-like receptors and cytokines, orchestrate inflammatory and fibrogenic cascades. Additionally, metabolic reprogramming, featuring aerobic glycolysis and altered lipid/amino acid metabolism, further exacerbates fibrosis. Despite advancements in understanding, there remain uncertainties regarding the optimal therapeutic strategies. Emerging research highlights the potential of targeting gut microbiota restoration, immune modulation, and metabolic interventions. This review comprehensively summarizes the current understanding of gut-liver axis-driven hepatic fibrosis, critically analyzing therapeutic opportunities to provide valuable insights for researchers and clinicians.