Aflatoxin B1 Induces Inflammatory Liver Injury via Gut Microbiota in Mice.
Aflatoxin B1 Induces Inflammatory Liver Injury via Gut Microbiota in Mice.
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DOI：
10.1021/acs.jafc.3c02617
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发表时间：
2023-07
影响因子：
6.1
通讯作者：
Lin Ye;Huodai Chen;K. Tsim;Xing Shen;Xiangmei Li;Xueling Li;Hongtao Lei;Yunle Liu
中科院分区：
文献类型：
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作者：
Lin Ye;Huodai Chen;K. Tsim;Xing Shen;Xiangmei Li;Xueling Li;Hongtao Lei;Yunle Liu
黄曲霉毒素B1(AFB1)是一种有效的食源性肝癌致癌物，是引起人和动物肝脏损伤的毒性最大的黄曲霉毒素。黄曲霉毒素的物种特异性敏感性不能完全用动物物种间黄曲霉毒素1代谢的差异来解释。肠道微生物区系在炎症性肝损伤中起关键作用，但肠道微生物区系在黄曲霉毒素B_1诱导的肝损伤中的作用仍有待揭示。在这里，给小鼠灌胃黄曲霉毒素1 28天。然后分析肠道微生物区系、结肠屏障、肝脏下垂和炎症的调节。为了进一步验证肠道微生物区系在黄曲霉毒素B_1诱导的肝损伤中的直接作用，用抗生素混合物(ABX)去除肠道微生物区系，并进行粪便微生物区系移植(FMT)。AFB1对小鼠的治疗改变了肠道微生物区系组成，如增加类杆菌、副杆菌和乳杆菌的相对丰度，导致结肠屏障功能障碍和促进肝脏热下垂。在ABX治疗的小鼠中，AFB1对结肠屏障和肝脏下垂几乎没有影响。值得注意的是，在FMT后，小鼠被AFB1处理的小鼠的肠道微生物区系定植，结肠屏障功能障碍，以及肝脏下垂和炎症被明显识别出来。我们认为肠道微生物区系直接参与了黄曲霉毒素B_1诱导的肝脏下垂和炎症。这些结果为AFB1肝毒性的机制提供了新的见解，并为预防或减轻AFB1肝毒性的新的靶向干预铺平了窗口。
Aflatoxin B1 (AFB1), 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 AFB1 between animal species. The gut microbiota are critical in inflammatory liver injury, but it remains to reveal the role of gut microbiota in AFB1-induced liver injury. Here, mice were gavaged with AFB1 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 AFB1-induced liver injury, mice were treated with antibiotic mixtures (ABXs) to deplete the microbiota, and fecal microbiota transplantation (FMT) was conducted. The treatment of AFB1 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, AFB1 had little effect on the colonic barrier and liver pyroptosis. Notably, after FMT, in which the mice were colonized with gut microbiota from AFB1-treated mice, colonic barrier dysfunction, and liver pyroptosis and inflammation were obliviously identified. We proposed that the gut microbiota directly participated in AFB1-induced liver pyroptosis and inflammation. These results provide new insights into the mechanisms of AFB1 hepatotoxicity and pave a window for new targeted interventions to prevent or reduce AFB1 hepatotoxicity.