Aflatoxin B₁ Induces Inflammatory Liver Injury via Gut Microbiota in Mice

Abstract

Aflatoxin B 1 (AFB 1 ), 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 1 between animal species. The gut microbiota are critical in inflammatory liver injury, but it remains to reveal the role of gut microbiota in AFB 1 -induced liver injury. Here, mice were gavaged with AFB 1 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 1induced liver injury, mice were treated with antibiotic mixtures (ABXs) to deplete the microbiota, and fecal microbiota transplantation (FMT) was conducted. The treatment of AFB 1 in mice altered gut microbiota composition, such as increasing the relative abundance of Bacteroides, Parabacteroides, and Lactobacillus, inducing colonic barrier dysfunction and promoting liver pyroptosis. In ABX-treated mice, AFB 1 had little effect on the colonic barrier and liver pyroptosis. Notably, after FMT, in which the mice were colonized with gut microbiota from AFB 1 -treated mice, colonic barrier dysfunction, and liver pyroptosis and inflammation were obliviously identified. We proposed that the gut microbiota directly participated in AFB 1 -induced liver pyroptosis and inflammation. These results provide new insights into the mechanisms of AFB 1 hepatotoxicity and pave a window for new targeted interventions to prevent or reduce AFB 1 hepatotoxicity.

Aflatoxin B1 exposure causes splenic pyroptosis by disturbing the gut microbiota-immune axis

“…39 The disrupted intestinal barrier after exposure to AFB 1 was reported in our previous work. 40 Furthermore, AFB 1 increased intestinal permeability in mice (data not shown). Hence, AFB 1 may potentially alter the gut microbiota through its gut toxicity, which includes the disruption of the intestinal barrier and the leakage of antimicrobial substances.…”

Assessment of the Impact of Humic Acids on Intestinal Microbiota, Gut Integrity, Ileum Morphometry, and Cellular Immunity of Turkey Poults Fed an Aflatoxin B1-Contaminated Diet

“…This disruption often leads to an overgrowth of Proteobacteria, a group of typically Gram-negative bacteria that are not typically dominant in a healthy chicken gut. Moreover, AFB 1 exposure triggers a stress response in chickens, leading to immune suppression and inflammation [ 27 ]. This weakened immune system becomes less efficient in controlling the growth of opportunistic pathogens like Proteobacteria, which can readily exploit the situation and proliferate, causing dysbacteriosis and intestinal inflammation; these are commonly associated with increased permeability and chronic systemic inflammation [ 28 ].…”

Lycopene as a Therapeutic Agent against Aflatoxin B1-Related Toxicity: Mechanistic Insights and Future Directions

“…Prior investigations have demonstrated that exposure to AFB1 can activate an inflammatory response [72,[100][101][102]. Epidemiological studies have established a positive association between AFB1 exposure and various chronic diseases, such as neurodegenerative disease, chronic enteritis, and liver cancer [16,100,103,104].…”