The role of gut microbiota in liver regeneration after partial hepatectomy: new evidence from animal and human studies

Liver regeneration is increasingly recognized as a process influenced not only by hepatocellular signaling but also by the gut-liver axis, where gut microbiota-derived metabolites, immune mediators, and extracellular vesicles modulate hepatic recovery after liver damage. In this review, we explore recent progress in understanding the gut microbiota's role in liver regeneration and discuss its therapeutic potential in the context of hepatic surgery and liver transplantation. Emerging evidence shows that beneficial microbial taxa, including Akkermansia muciniphila, Bifidobacterium longum, and Parabacteroides distasonis, enhance liver regeneration by regulating short-chain fatty acid production, bile acid metabolism, and tricarboxylic acid cycle pathways, while dysbiosis and microbial translocation can impair regenerative outcomes. Key host-microbiome interactions, particularly the Farnesoid X Receptor (FXR)-Fibroblast Growth Factor 19 (FGF19) signaling axis, play a central role in protecting hepatocytes from bile acid overload and supporting regeneration, highlighting the therapeutic potential of FXR agonists, FGF19 mimetics, probiotics, dietary interventions, and metabolite supplementation. At the same time, monitoring bile acids profiles alongside gut microbiota composition may allow early detection and prevention of complications. In addition, microbial-derived markers such as the lipopolysaccharide/lipoteichoic acid ratio may serve as predictive biomarkers for post-hepatectomy liver failure. Adjunctive approaches, including vitamin D supplementation, may further support regeneration through vitamin D receptor-mediated regulation of bile acid homeostasis and cell-cycle progression. In the context of live donor liver transplantation, the detection of occult bacteremia further underscores the complexity of host-microbiome interactions and suggests that microbiological surveillance could improve postoperative management. Collectively, these findings emphasize the importance of microbiota-targeted strategies to improve hepatic regeneration, reduce postoperative complications, and optimize outcomes following liver surgery and transplantation.