Abstract：
Chlorinated polyfluorinated ether sulfonate (F-53B), a substitute of perfluorooctane sulfonic acid (PFOS), has attracted significant attention for its link to hepatotoxicity and enterotoxicity. Nevertheless, the underlying mechanisms of F-53B-induced enterohepatic toxicity remain incompletely understood. This study aimed to explore the role of F-53B exposure on enterohepatic injury based on the gut microbiota, pathological and molecular analysis in mice. Here, we exposed C57BL/6 mice to F-53B (0, 4, 40, and 400 μg/L) for 28 days. Our findings revealed a significant accumulation of F-53B in the liver, followed by small intestines, and feces. In addition, F-53B induced pathological collagen fiber deposition and lipoid degeneration, up-regulated the expression of fatty acid β-oxidation-related genes (PPARα and PPARγ, etc), while simultaneously down-regulating pro-inflammatory genes (Nlrp3, IL-1β, and Mcp1) in the liver. Meanwhile, F-53B induced ileal mucosal barrier damage, and an up-regulation of pro-inflammatory genes and mucosal barrier-related genes (Muc1, Muc2, Claudin1, Occludin, Mct1, and ZO-1) in the ileum. Importantly, F-53B distinctly altered gut microbiota compositions by increasing the abundance of Akkermansia and decreasing the abundance of Prevotellaceae_NK3B31_group in the feces. F-53B-altered microbiota compositions were significantly associated with genes related to fatty acid β-oxidation, inflammation, and mucosal barrier. In summary, our results demonstrate that F-53B is capable of inducing hepatic injury, ileitis, and gut microbiota dysbiosis in mice, and the gut microbiota dysbiosis may play an important role in the F-53B-induced enterohepatic toxicity.
摘要：
氯化聚氟醚磺酸盐(F-53B),全氟辛烷磺酸（PFOS）的替代品，因其与肝毒性和肠毒性的联系而引起了广泛关注。然而，F-53B诱导的肝肠毒性的潜在机制尚不完全清楚.本研究以肠道菌群为基础,探讨F-53B暴露在肝损伤中的作用,小鼠的病理和分子分析。这里,我们将C57BL/6小鼠暴露于F-53B（0、4、40和400μg/L）28天。我们的发现揭示了F-53B在肝脏中的大量积累，其次是小肠，还有粪便.此外,F-53B诱导病理性胶原纤维沉积和类脂变性,上调脂肪酸β-氧化相关基因(PPARα和PPARγ，etc),同时下调促炎基因(Nlrp3，IL-1β，和Mcp1）在肝脏中。同时,F-53B诱导回肠黏膜屏障损伤,以及促炎基因和粘膜屏障相关基因的上调(Muc1，Muc2，Claudin1，Occludin，回肠中的Mct1和ZO-1）。重要的是,F-53B通过增加粪便中Akkermansia的丰度和减少Prevotellaceae_NK3B31_组的丰度，明显改变了肠道菌群组成。F-53B改变的微生物群组成与脂肪酸β-氧化相关的基因显着相关，炎症,和粘膜屏障。总之,我们的结果表明，F-53B能够诱导肝损伤，ileitis,和小鼠的肠道微生物群失调，肠道菌群失调可能在F-53B诱导的肠肝毒性中起重要作用。
