Microbiome and gut-liver interactions: From mechanisms to therapies

Abstract

The gut-liver axis represents a bidirectional and dynamic communication system between the gastrointestinal tract and liver, critically modulated by gut microbiota, bile acids, immune responses, and metabolic pathways. Disruption of this finely tuned axis contributes to the pathogenesis of several liver diseases, including alcohol-associated hepatitis, metabolic dysfunction-associated steatotic liver disease, cirrhosis, hepatic encephalopathy, and cholangiopathies like primary biliary cholangitis and primary sclerosing cholangitis. Dysbiosis, marked by reduced microbial diversity and dominance of pathogenic species, alters bile acid metabolism, increases gut permeability, and fuels hepatic inflammation. In cholangiopathies, the gut microbiome modulates immune dysregulation and fibrosis through complex microbial-host interactions. Emerging therapies targeting the microbiota, such as fecal microbiota transplantation, antibiotics (e.g., rifaximin, vancomycin), bile acid modulators, and probiotics, show promise in restoring microbial equilibrium, improving liver biochemistry, and reducing disease progression. Precision medicine strategies integrating genomics, metabolomics, and microbiomics offer a tailored approach for therapy and prognosis. This review highlights the central role of the gut-liver axis in liver diseases and the potential of microbiome-based interventions to shift management from symptomatic relief toward disease modification and personalized hepatology, underscoring a new frontier in liver disease therapeutics.

Keywords: Microbiome; Hepatic encephalopathy; Steatotic liver disease; Fecal microbiota transplantation; Cholangiopathies

Core Tip: The gut-liver axis is emerging as a key player in chronic liver disease pathogenesis and treatment. From alcoholic hepatitis to cholangiopathies like primary biliary cholangitis and primary sclerosing cholangitis, disruptions in the gut microbiota fuel liver inflammation, fibrosis, and immune dysregulation. This review explores how targeting the microbiome through fecal microbiota transplantation, bile acid modulators, and precision medicine can transform liver disease management. With growing evidence supporting microbiome-based interventions, this article offers a compelling look into how restoring gut-liver harmony may shift treatment from symptom control to disease reversal, unlocking the future of personalized hepatology.