Oduyebo Ibironke, Camilleri Michael
Division of Gastroenterology and Hepatology, Mayo Clinic, Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Rochester, Minnesota, USA.
Curr Opin Gastroenterol. 2017 May;33(3):189-195. doi: 10.1097/MOG.0000000000000344.
Our objective was to review advances in bile acids in health and disease published in the last 2 years. Bile acid diarrhea (BAD) is recognized as a common cause of chronic diarrhea, and its recognition has been facilitated by development of new screening tests.
Primary BAD can account for 30% of cases of chronic diarrhea. The mechanisms leading to BAD include inadequate feedback regulation by fibroblast growth factor 19 (FGF-19) from ileal enterocytes, abnormalities in synthesis or degradation of proteins involved in FGF-19 regulation in hepatocytes and variations as a function of the bile acid receptor, TGR5 (GPBAR1). SeHCAT is the most widely used test for diagnosis of BAD. There has been significant validation of fasting serum FGF-19 and 7 α-hydroxy-cholesten-3-one (C4), a surrogate measure of bile acid synthesis. Bile acid sequestrants are the primary treatments for BAD; the farnesoid X-receptor-FGF-19 pathway provides alternative therapeutic targets for BAD. Bile acid-stimulated intestinal mechanisms contribute to the beneficial effects of bariatric surgery on obesity, glycemic control and the treatment of recurrent Clostridium difficile infection.
Renewed interest in the role of bile acids is leading to novel management of diverse diseases besides BAD.
我们的目标是回顾过去两年发表的关于健康与疾病中胆汁酸的研究进展。胆汁酸腹泻(BAD)被认为是慢性腹泻的常见原因,新筛查试验的发展有助于对其进行识别。
原发性BAD可占慢性腹泻病例的30%。导致BAD的机制包括回肠肠细胞中成纤维细胞生长因子19(FGF - 19)的反馈调节不足、肝细胞中参与FGF - 19调节的蛋白质合成或降解异常以及作为胆汁酸受体TGR5(GPBAR1)功能的变异。SeHCAT是诊断BAD最广泛使用的检测方法。空腹血清FGF - 19和7α - 羟基胆甾 - 3 - 酮(C4,胆汁酸合成的替代指标)已得到大量验证。胆汁酸螯合剂是BAD的主要治疗方法;法尼酯X受体 - FGF - 19途径为BAD提供了替代治疗靶点。胆汁酸刺激的肠道机制有助于减肥手术对肥胖、血糖控制和复发性艰难梭菌感染治疗的有益作用。
对胆汁酸作用的重新关注正在导致除BAD之外的多种疾病的新管理方法。