Gut microbiota-derived extracellular vesicles in sepsis-associated liver injury: emerging mediators of gut-liver axis dysfunction

Sepsis is a life-threatening syndrome of multiple organ dysfunction driven by a dysregulated host response to infection. Its high mortality is closely associated with disruption of gut-liver axis homeostasis. Gut microbiota-derived extracellular vesicles (GM-EVs) have emerged as important mediators of cross-kingdom communication and molecular exchange between intestinal microbes and the host. Accumulating evidence highlights their regulatory role in the progression of sepsis-associated gut-liver axis dysfunction. This review systematically summarizes the biogenesis of GM-EVs and the regulation of their release under septic conditions, as well as the mechanisms underlying their transport across the impaired intestinal epithelial barrier. We further elaborate on the pathological effects of GM-EVs in the liver, including amplification of hepatic inflammatory cascades, disruption of intrahepatic immune homeostasis, reprogramming of hepatic metabolism, and induction of hepatocellular injury and programmed cell death. Additionally, we discuss the translational potential of strategies targeting GM-EVs for the prevention and treatment of sepsis. Finally, we examine current research limitations and future directions, with a focus on the potential of GM-EVs as biomarkers and therapeutic targets for the early detection and precision management of sepsis-associated liver injury.