黄曲霉毒素 B1 通过扰乱肠道微生物群-胆汁酸-FXR 轴诱导小鼠肝损伤。

Aflatoxin B1 induces liver injury by disturbing gut microbiota-bile acid-FXR axis in mice.

机构信息

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.

出版信息

Food Chem Toxicol. 2023 Jun;176:113751. doi: 10.1016/j.fct.2023.113751. Epub 2023 Apr 6.

DOI:10.1016/j.fct.2023.113751

PMID:37030333

Abstract

Aflatoxin B1 (AFB1) is one of major pollutant in food and feed worldwide. The purpose of this study is to investigate the mechanism of AFB1-induced liver injury. Our results showed that AFB1 caused hepatic bile duct proliferation, oxidative stress, inflammation and liver injury in mice. AFB1 exposure induced gut microbiota dysbiosis and reduced fecal bile salt hydrolase (BSH) activity. AFB1 exposure promoted hepatic bile acid (BA) synthesis and changed intestinal BA metabolism, especially increased intestinal conjugated bile acids levels. AFB1 exposure inhibited intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) signaling. Furthermore, the mice received fecal microbiota transplantation from AFB1-treated mice induced liver injury, reduced intestinal FXR signaling and increased hepatic BA synthesis. Finally, the intestine-restricted FXR agonist treatment decreased hepatic BA synthesis, ROS level, inflammation and liver injury in AFB1-treated mice. This study suggests that modifying the gut microbiota, altering intestinal BA metabolism and/or activating intestinal FXR/FGF-15 signaling may be of value for the treatment of AFB1-induced liver disease.

摘要

黄曲霉毒素 B1（AFB1）是全球食品和饲料中的主要污染物之一。本研究旨在探讨 AFB1 诱导肝损伤的机制。我们的结果表明，AFB1 可导致小鼠肝内胆管增生、氧化应激、炎症和肝损伤。AFB1 暴露可诱导肠道微生物群失调，并降低粪便胆盐水解酶（BSH）活性。AFB1 暴露促进了肝胆汁酸（BA）的合成，并改变了肠道 BA 代谢，特别是增加了肠道结合型胆汁酸水平。AFB1 暴露抑制了肠道法尼醇 X 受体（FXR）/成纤维细胞生长因子 15（FGF-15）信号。此外，接受来自 AFB1 处理小鼠的粪便微生物群移植的小鼠可诱导肝损伤，降低肠道 FXR 信号并增加肝 BA 合成。最后，肠道特异性 FXR 激动剂治疗可降低 AFB1 处理小鼠的肝 BA 合成、ROS 水平、炎症和肝损伤。本研究表明，改变肠道微生物群、改变肠道 BA 代谢和/或激活肠道 FXR/FGF-15 信号可能有助于治疗 AFB1 诱导的肝病。