Extracellular Vesicle Function in the Gut–Liver Axis: Dual Role in Disease Pathogenesis and Therapeutic Potential

Background/Objectives: The liver is responsible for crucial functions such as digestion, metabolism, detoxification, and immune regulation. These roles are severely compromised in chronic liver diseases, which affect 1.7 billion people globally and cause 1.4 million annual deaths and include conditions such as metabolic dysfunction-associated steatohepatitis, alcohol-associated liver disease, and primary sclerosing cholangitis. This review summarizes the evidence for extracellular vesicles (EVs) as mediators within the gut–liver axis that promote or alleviate disease in each organ system. Methods: Literature searches were conducted in PubMed, PMC, and Google Scholar for English-language publications between February and October 2026, with the final search performed in October 2026. Studies published from 1964 to April 2026 were considered. Keywords combined via Boolean operators included liver diseases (MASLD, MASH, AALD, PSC), intestinal conditions (IBD, gut dysbiosis, hepatic injury), and vesicle types (exosome, EV, bacterial, food-derived, probiotic, engineered, biliary, EV-based therapy). For this narrative review, preclinical and translational studies focusing on EV biogenesis, biodistribution, and roles along the axis were critically evaluated and selected. Results: The gut–liver axis enables EV-mediated molecular communication between the gut epithelial barrier, microbiota, and liver. Prokaryotic, eukaryotic or food-derived EVs serve as long-distance signaling vehicles, protecting complex molecular cargo from degradation during transport between producer and recipient cells. While these EVs exert divergent effects—accelerating disease progression or offering protective properties—evidence demonstrating EV trafficking from gut to liver is substantially more robust than evidence supporting transport from liver to gut. Conclusions: EVs are functional components of the gut–liver axis that regulate organ injury and offer therapeutic leads. However, the current evidence remains predominantly preclinical; physiological proof of direct EV traversal between these organs is lacking and requires experimental validation.