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

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.

Automated summary

This study investigated the mechanism of AFB1-induced liver injury. It was found that AFB1 exposure caused bile duct proliferation, oxidative stress, inflammation, and liver injury in mice. AFB1 exposure also led to gut microbiota dysbiosis and reduced fecal bile salt hydrolase activity. Furthermore, AFB1 exposure altered intestinal bile acid metabolism and inhibited intestinal FXR/FGF-15 signaling. The study suggests that modifying the gut microbiota, altering intestinal bile acid metabolism, and activating intestinal FXR/FGF-15 signaling may be potential treatment strategies for AFB1-induced liver disease.