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

• Published in: Food and chemical toxicology 2023-06, Vol.176, p.113751-113751, Article 113751
• Main Authors: Liu, Yunhuan, Li, Jinyan, Kang, Weili, Liu, Shuiping, Liu, Jinyan, Shi, Mengdie, Wang, Yubo, Liu, Xianjiao, Chen, Xingxiang, Huang, Kehe
• Format: Article
• Language: English
• Subjects: AFB1; Aflatoxin B1 - metabolism; Aflatoxin B1 - toxicity; Animals; Bile acids; Bile Acids and Salts - metabolism; Chemical and Drug Induced Liver Injury, Chronic - metabolism; FXR/FGF-15; Gastrointestinal Microbiome; Gut microbiota; Inflammation - metabolism; Liver - metabolism; Liver injury; Mice; Mice, Inbred C57BL
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2023.113751

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. [Display omitted] •AFB1 induces hepatic ductular proliferation, oxidative stress, inflammation and injury in mice.•AFB1 exposure induces gut microbiota dysbiosis and hepatic bile acid accumulation.•Gut microbiota–bile acid–intestinal FXR signaling is involved in AFB1-induced liver injury.•Activation of intestinal FXR signaling reduced hepatic bile acid synthesis in AFB1-exposed mice.•Activation of intestinal FXR signaling improved liver injury in AFB1-exposed mice.