Siddle Matthew, Gallego Durán Rocío, Goel Deepika, Renquist Benjamin J, Holt Marie K, Hadjihambi Anna
Roger Williams Institute of Liver Studies, School of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, Foundation for Liver Research and King's College Hospital, London, UK.
UCM Digestive Diseases, Virgen del Rocío University Hospital, Instituto de Biomedicina de Sevilla (HUVR/CSIC/US), Department of Medicine, University of Seville, Seville, Spain.
Nat Rev Gastroenterol Hepatol. 2025 Nov 10. doi: 10.1038/s41575-025-01142-z.
The liver is a metabolically flexible tissue, adapting its functions to changes in nutrient availability and physiological states. This adaptability is crucial for maintaining metabolic homeostasis and likely involves communication with the central nervous system through the liver-brain axis. The liver also receives a constant influx of nutrients, hormones and microbial metabolites from the gastrointestinal tract in a multifaceted communication network, the gut-liver-brain axis. Dysregulation of this communication can lead to hepatic encephalopathy and cognitive impairments in early-stage chronic liver disease, such as metabolic dysfunction-associated steatotic liver disease, substantially affecting patient quality of life. This Review examines key signalling pathways along the liver-brain axis: humoral signalling, including metabolites, hepatokines, toxins and inflammation, and neural pathways, focusing on afferent signalling through the common hepatic branch of the vagus nerve. We discuss how each pathway might contribute to behavioural and mood changes in chronic liver disease and the development of hepatic encephalopathy. Although the humoral effects have been studied more extensively, we propose that the afferent vagus nerve is central to liver disease-associated cognitive and behavioural complications. Finally, we highlight how new techniques and tools could advance our understanding of the gut-liver-brain communication that affects behaviour.
肝脏是一种代谢适应性强的组织，能使其功能适应营养物质供应和生理状态的变化。这种适应性对于维持代谢稳态至关重要，并且可能涉及通过肝-脑轴与中枢神经系统进行交流。肝脏还在一个多方面的交流网络——肠-肝-脑轴中，持续接收来自胃肠道的营养物质、激素和微生物代谢产物。这种交流的失调可导致肝性脑病以及早期慢性肝病（如代谢功能障碍相关脂肪性肝病）中的认知障碍，严重影响患者的生活质量。本综述探讨了肝-脑轴上的关键信号通路：体液信号通路，包括代谢产物、肝细胞因子、毒素和炎症，以及神经通路，重点关注通过迷走神经肝总分支的传入信号。我们讨论了每条通路如何可能导致慢性肝病中的行为和情绪变化以及肝性脑病的发展。尽管对体液效应的研究更为广泛，但我们认为传入迷走神经是肝病相关认知和行为并发症的核心。最后，我们强调新技术和工具如何能够推进我们对影响行为的肠-肝-脑交流的理解。
