Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Am J Physiol Gastrointest Liver Physiol. 2020 Nov 1;319(5):G619-G625. doi: 10.1152/ajpgi.00308.2020. Epub 2020 Sep 16.
The enterohepatic circulation of bile acids comprises a tightly regulated process of hepatic bile acid secretion, intestinal reabsorption and transport back to the liver. Disruption of this process has significant consequences for gastrointestinal, liver and whole body homeostasis and therefore offers opportunities for therapeutic intervention. In this review we discuss the effects of (pharmacological) interruption of the enterohepatic circulation at different levels. Recently, several studies have been published on ileal interruption of the enterohepatic circulation of bile acids, targeting the apical-sodium dependent bile acid transporter (ASBT, ), as therapy for various diseases. However, ambiguous results have been reported and in-depth mechanistic insights are lacking. Here we discuss these novel studies and review the current knowledge on the consequences of ASBT inhibition and its potential effects on physiology and metabolism.
胆汁酸的肠肝循环包括一个受严格调控的过程,即肝脏胆汁酸分泌、肠道重吸收和运输回肝脏。该过程的破坏会对胃肠道、肝脏和全身的稳态产生重大影响,因此为治疗干预提供了机会。在这篇综述中,我们讨论了在不同水平上(药理学)中断肠肝循环的影响。最近,有几项关于回肠胆汁酸肠肝循环中断的研究发表,针对顶端钠依赖性胆汁酸转运体(ASBT,),作为治疗各种疾病的方法。然而,报道的结果并不明确,缺乏深入的机制见解。在这里,我们讨论这些新的研究,并回顾 ASBT 抑制的后果及其对生理学和新陈代谢的潜在影响的现有知识。