Liver-nervous system axis: pathways, dysregulation, and translational perspectives

The liver and the nervous system form a dynamic bidirectional regulatory network through the liver-nervous system axis, which is crucial for maintaining metabolic homeostasis, immune balance, and the integrity of neural function in the body. However, the specific regulatory pathways between the liver and the nervous system, as well as their mechanisms in the development and progression of diseases, remain incompletely understood. Moreover, the dynamic regulatory mechanisms of the blood-brain barrier in the transport of liver metabolites are yet to be elucidated. Therefore, we have integrated the latest research advances in recent years in the fields of liver innervation, the neuroregulatory effects of liver-derived substances, and the trans-organ conduction of inflammatory mediators. Additionally, we incorporate clinical translational evidence from the application of β-blockers, vagus nerve stimulation, liver transplantation, and other interventions to systematically elucidate the coordinated regulatory patterns of the liver and the nervous system under physiological conditions, as well as the mechanisms of interactive disorders under pathological conditions. The aim is to clarify the interactions between the liver and the nervous system and their significance in physiological and pathological processes, thus providing a theoretical basis and potential therapeutic targets for future related research.