Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.
Food Funct. 2024 Nov 25;15(23):11432-11443. doi: 10.1039/d4fo03353a.
Fructooligosaccharide (FOS) is a widely used prebiotic and health food ingredient, but few reports have focused on its risk to specific populations. Recently, it has been shown that the intake of inulin, whose main component is FOS, can lead to cholestasis and induce hepatocellular carcinoma in mice fed a high-fat diet (HFD); however, the molecular mechanism behind this is not clear. This study found that FOS supplementation induced abnormal enterohepatic circulation of bile acids in HFD-fed mice, which showed a significant increase in bile acid levels in the blood and liver, especially the secondary bile acids with high cytotoxicity, such as deoxycholic acid. The abundance of , , and other bacteria in the gut microbiota also increased significantly. The analysis of the signaling pathway involved in regulating the enterohepatic circulation of bile acids showed that the weakening of the feedback inhibition of FXR-FGF15 and FXR-SHP signalling pathways possibly induced the enhancement of CYP7A1 activity and bile acid reabsorption in the blood and liver and led to an increase in bile acid synthesis and accumulation in the liver, increasing the risk of cholestasis. This study showed the risk of health damage caused by FOS supplementation in HFD-fed mice, which is caused by gut microbiota dysfunction and abnormal enterohepatic circulation of bile acids. Therefore, the application of FOS should be standardized to avoid the health risks of unreasonable FOS use in specific populations.
果寡糖（FOS）是一种广泛应用的益生元和保健品成分，但很少有报道关注其对特定人群的风险。最近的研究表明，菊粉（其主要成分为 FOS）的摄入会导致高脂肪饮食（HFD）喂养的小鼠发生胆汁淤积，并诱导肝细胞癌；然而，其背后的分子机制尚不清楚。本研究发现，FOS 补充剂会诱导 HFD 喂养小鼠胆汁酸的异常肠肝循环，导致血液和肝脏中的胆汁酸水平显著升高，特别是具有高细胞毒性的次级胆汁酸，如脱氧胆酸。肠道微生物群中， 、 等细菌的丰度也显著增加。对调节胆汁酸肠肝循环的信号通路的分析表明，FXR-FGF15 和 FXR-SHP 信号通路的反馈抑制减弱可能诱导 CYP7A1 活性增强和血液及肝脏中胆汁酸重吸收增加，导致胆汁酸合成和在肝脏中积累增加，增加胆汁淤积的风险。本研究表明，FOS 补充剂在 HFD 喂养小鼠中会引起健康损害，这是由肠道微生物群功能障碍和胆汁酸的异常肠肝循环引起的。因此，应该规范 FOS 的应用，以避免在特定人群中不合理使用 FOS 带来的健康风险。
