Aflatoxin B Induces Inflammatory Liver Injury via Gut Microbiota in Mice.

Aflatoxin B (AFB), a potent food-borne hepatocarcinogen, is the most toxic aflatoxin that induces liver injury in humans and animals. Species-specific sensitivities of aflatoxins cannot be fully explained by differences in the metabolism of AFB between animal species. The gut microbiota are critical in inflammatory liver injury, but it remains to reveal the role of gut microbiota in AFB-induced liver injury. Here, mice were gavaged with AFB for 28 days. Then, the modulation of gut microbiota, colonic barrier, and liver pyroptosis and inflammation were analyzed. To further verify the direct role of gut microbiota in AFB-induced liver injury, mice were treated with antibiotic mixtures (ABXs) to deplete the microbiota, and fecal microbiota transplantation (FMT) was conducted. The treatment of AFB in mice altered gut microbiota composition, such as increasing the relative abundance of , , and , inducing colonic barrier dysfunction and promoting liver pyroptosis. In ABX-treated mice, AFB had little effect on the colonic barrier and liver pyroptosis. Notably, after FMT, in which the mice were colonized with gut microbiota from AFB-treated mice, colonic barrier dysfunction, and liver pyroptosis and inflammation were obliviously identified. We proposed that the gut microbiota directly participated in AFB-induced liver pyroptosis and inflammation. These results provide new insights into the mechanisms of AFB hepatotoxicity and pave a window for new targeted interventions to prevent or reduce AFB hepatotoxicity.