Implications of gut microbiota in hepatic and pancreatic diseases: Gut-liver-pancreas axis

Abstract

The gut–liver-pancreas axis (GLPA) is a critical network shaped by gut microbiota (GM) and their metabolites, essential for maintaining metabolic and immune balance. Disruption of this microbial equilibrium, known as dysbiosis, contributes to the development and progression of various hepatic and pancreatic diseases. Through mechanisms such as increased intestinal permeability and exposure to microbial products-including lipopolysaccharide, trimethylamine-N-oxide, and secondary bile acids-dysbiosis promotes inflammation, oxidative stress, insulin resistance, and carcinogenesis. These changes are linked to conditions including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cirrhosis, hepatocellular carcinoma, pancreatitis, pancreatic ductal adenocarcinoma, and diabetes. Emerging tools like stool metagenomics and serum metabolomics help identify microbial biomarkers for diagnosis and risk stratification. While interventions such as probiotics, dietary changes, and fecal microbiota transplantation aim to restore microbial balance, their success remains inconsistent. This work aims to highlight the pathogenic role of GM across the GLPA, with special emphasis on the underexplored gut-pancreas connection. Advancing our understanding of the GLPA can unlock novel microbiota-targeted approaches for early diagnosis and treatment of hepatopancreatic diseases.

Keywords: Microbial metabolites; Dysbiosis; Immune modulation; Therapeutic strategies

Core Tip: This editorial highlights the central role of gut microbiota in regulating the gut-liver-pancreas axis, a dynamic network critical for metabolic and immune homeostasis. Dysbiosis-driven disruptions-via microbial metabolites, barrier dysfunction, and immune imbalance-underlie the pathogenesis of liver and pancreatic diseases. While gut-liver interactions are well studied, gut-pancreas crosstalk remains underexplored. We emphasize emerging biomarkers, microbial-based therapies, and the urgent need for longitudinal studies and metabolomic profiling to translate microbiome science into precision diagnostics and treatments for hepatopancreatic disorders.