肠-菌-肝轴及其在肠衰竭相关性肝损害发生发展中的作用

由于长期的肠道摄入不足,肠衰竭患者不得不依赖肠外营养(PN)来维持能量和正常的生理需求。然而PN在提供能量及营养物质的同时,也会引起肝脏损害。此外,由于肠道结构和内环境发生改变,IF患者往往伴随着肠道菌群失调及小肠细菌过度生长,过度生长的细菌代谢产生的毒性介质可诱导肠道炎性反应和胆汁酸代谢紊乱,最终导致肠黏膜屏障功能受损及肠衰竭相关性肝损害(IFALD)。自1998年Marshall首次提出肠-肝轴的概念以来,肠-肝轴紊乱在IFALD发生发展中的作用也备受关注。肠道-肝脏之间的"对话"是维持肝脏代谢和肠道内稳态平衡的关键,二者相互作用,互为因果。然而,作为一个"被遗忘的器官",肠道菌群在IFALD发病过程中的作用并没有得到很好的体现。因此,笔者首次提出肠-菌-肝轴这样一个全新的概念,试图强调肠道菌群是肠-肝轴中的重要一环,三者之间的相互作用在IF患者肠道和肝脏损害过程中扮演着重要的角色。对肠-菌-肝轴这一概念的理解和深入研究,将对理解IFALD的发病机制和改进防治措施具有重要意义。

Mechanism of gut-microbiota-liver axis in the pathogenesis of intestinal failure-associated liver disease

Intestinal failure(IF)is defined as the critical reduction of functional intestines below the minimum needed to absorb nutrients and fluids,so that intravenous supplementation with parenteral nutrition(PN)is required to maintain health and/or growth.Although the benefits are evident,patients receiving PN can suffer from serious cholestasis due to lack of enteral feeding and small intestinal bacterial overgrowth(SIBO).One such complication that may arise is intestinal failure-associated liver disease(IFALD).Evidences from recent studies suggest that alterations in the intestinal microbiota,as well as intraluminal bile acid driven signaling,may play a critical role in both hepatic and intestinal injury.Since Marshall first proposed the concept of the gut-liver axis in 1998,the role of gut-liver axis disorders in the development of IFALD has received considerable attention.The conversation between gut and liver is the key to maintain liver metabolism and intestinal homeostasis,which influences each other and is reciprocal causation.However,as a"forgotten organ",intestinal microbiota on the pathogenesis of IFALD has not been well reflected.As such,we propose,for the first time,the concept of gut-microbiota-liver axis to emphasize the importance of intestinal microbiota in the interaction of gut-liver axis.Analysis and research on gut-microbiota-liver axis will be of great significance for understanding the pathogenesis of IFALD and improving the prevention and treatment measures.