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胆汁酸与肠道癌变交汇处的肠道微生物群:一个古老的故事,却令人着迷。

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing.

机构信息

Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China.

Department of Pharmacy, General Hospital, Tianjin Medical University, Tianjin, China.

出版信息

Int J Cancer. 2020 Apr 1;146(7):1780-1790. doi: 10.1002/ijc.32563. Epub 2019 Jul 23.

Abstract

The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids-microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids-microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.

摘要

在过去的十年中,全世界结直肠癌(CRC)的发病率显著上升。据报道,胆汁酸代谢和肠道微生物群的改变在肠道癌变中起着至关重要的作用。大约有万亿细菌栖息在人类肠道中,并维持着宿主代谢的平衡。胆汁酸是在肝脏中合成并进一步由肠道微生物群代谢的众多代谢物之一,对于维持正常的肠道微生物群和脂质消化至关重要。已经报道了多种受体,如 FXR、GPBAR1、PXR、CAR 和 VDR,它们作为胆汁酸的传感器发挥作用。在这篇综述中,我们主要讨论了胆汁酸代谢和肠道微生物群在肠道癌变中的相互作用。然后,我们总结了涉及 CRC 的胆汁酸受体的关键作用,并讨论了通过调节胆汁酸-微生物群轴(如益生菌、二甲双胍、熊去氧胆酸和粪便微生物群移植)来管理 CRC 的多种干预措施的合理性。因此,通过靶向胆汁酸-微生物群轴可能为 CRC 的预防和治疗提供新的治疗模式。

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